Trial Outcomes & Findings for Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT) (NCT NCT00032487)

Last Updated: 2017-03-30

Results Overview

Myocardial infarction (MI), intervention for coronary artery or Peripheral Vascular Disease (PVD), severe inoperable Coronary Artery Disease (CAD), new or worsening Congestive Heart Failure (CHF), stroke, Cardiovascular (CV) death, or amputation for ischemic gangrene.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1791 participants

Primary outcome timeframe

Post baseline time to the first major macrovascular event up to 82 months

Results posted on

2017-03-30

Participant Flow

Twenty Veterans Affairs Medical Centers (VAMCs) were selected to participate in this cooperative study. The recruitment period was from 12/01/00 to 05/31/03.

A patient had to meet all the screening criteria for eligibility and had to sign a consent form with blood samples and meet all entry criteria for pre-randomization testing. Once the patient was deemed appropriate for the study, Hines completed the randomization assignment.

Participant milestones

Participant milestones
Measure	Standard Glycemic Control Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs	Intensive Glycemic Control Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1
Overall Study STARTED	899	892
Overall Study COMPLETED	760	772
Overall Study NOT COMPLETED	139	120

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard Glycemic Control Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs	Intensive Glycemic Control Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1
Overall Study Withdrawal by Subject	67	43
Overall Study Adverse Event	3	7
Overall Study Lost to Follow-up	57	58
Overall Study Had other reason	12	12

Baseline Characteristics

Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1/Standard Glycemic Control n=899 Participants Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs	Arm 2/Intensive Glycemic Control n=892 Participants Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Standard glycemic control	Total n=1791 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	606 Participants n=99 Participants	612 Participants n=107 Participants	1218 Participants n=206 Participants
Age, Categorical >=65 years	293 Participants n=99 Participants	280 Participants n=107 Participants	573 Participants n=206 Participants
Age, Continuous	60.3 years STANDARD_DEVIATION 9.0 • n=99 Participants	60.5 years STANDARD_DEVIATION 9.0 • n=107 Participants	60.4 years STANDARD_DEVIATION 9.0 • n=206 Participants
Sex: Female, Male Female	26 Participants n=99 Participants	26 Participants n=107 Participants	52 Participants n=206 Participants
Sex: Female, Male Male	873 Participants n=99 Participants	866 Participants n=107 Participants	1739 Participants n=206 Participants
Region of Enrollment United States	899 participants n=99 Participants	892 participants n=107 Participants	1791 participants n=206 Participants

PRIMARY outcome

Timeframe: Post baseline time to the first major macrovascular event up to 82 months

Outcome measures

Outcome measures
Measure	Arm 1 n=899 Participants Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs	Arm 2 n=892 Participants Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1
Primary Major Macrovascular Events	264 participants	235 participants

SECONDARY outcome

Timeframe: Post baseline time to first event up to 82 months

New or worsening angina, new transient ischemic attack (TIA), new intermittent claudication or critical limb ischemia with Doppler evidence or total mortality.

Outcome measures

Outcome measures
Measure	Arm 1 n=899 Participants Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs	Arm 2 n=892 Participants Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1
Secondary Endpoint	283 participants	312 participants

Adverse Events

Arm 1

Serious events: 144 serious events

Other events: 730 other events

Deaths: 0 deaths

Arm 2

Serious events: 197 serious events

Other events: 675 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Project Manager

Hines CSPCC

Phone: 708-202-5785

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm 1 n=899 participants at risk Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs	Arm 2 n=892 participants at risk Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1
Infections and infestations Infections and infestations	9.0% 81/899 • Number of events 81 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	8.0% 71/892 • Number of events 71 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Cardiac disorders Cardiac disorders	4.0% 36/899 • Number of events 36 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	4.5% 40/892 • Number of events 40 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	2.2% 20/899 • Number of events 20 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	4.3% 38/892 • Number of events 38 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Gastrointestinal disorders Gastrointestinal disorders	4.4% 40/899 • Number of events 40 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	4.1% 37/892 • Number of events 37 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
General disorders General Disorders	3.6% 32/899 • Number of events 32 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	4.0% 36/892 • Number of events 36 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Nervous system disorders Nervous System Disorders	3.2% 29/899 • Number of events 29 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	4.0% 36/892 • Number of events 36 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal Disorders	2.8% 25/899 • Number of events 25 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	4.0% 36/892 • Number of events 36 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Surgical and medical procedures Surgical and Medical Procedures	4.1% 37/899 • Number of events 37 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	3.7% 33/892 • Number of events 33 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Metabolism and nutrition disorders Metabolism and Nutrition Disorders	2.8% 25/899 • Number of events 25 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	3.0% 27/892 • Number of events 27 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	3.4% 31/899 • Number of events 31 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	2.9% 26/892 • Number of events 26 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Renal and urinary disorders Renal and Urinary Disorders	2.8% 25/899 • Number of events 25 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	2.9% 26/892 • Number of events 26 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified	2.8% 25/899 • Number of events 25 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	2.6% 23/892 • Number of events 23 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Investigations Investigations	2.4% 22/899 • Number of events 22 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	2.5% 22/892 • Number of events 22 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Vascular disorders Vascular Disorders	2.4% 22/899 • Number of events 22 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	2.2% 20/892 • Number of events 20 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Blood and lymphatic system disorders Blood and lymphatic Disorders	1.3% 12/899 • Number of events 12 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	1.7% 15/892 • Number of events 15 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue Disorders	0.44% 4/899 • Number of events 4 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	1.3% 12/892 • Number of events 12 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Hepatobiliary disorders Hepatobiliary Disorders	0.67% 6/899 • Number of events 6 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	1.0% 9/892 • Number of events 9 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Psychiatric disorders Psychiatric Disorders	1.6% 14/899 • Number of events 14 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	0.78% 7/892 • Number of events 7 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Reproductive system and breast disorders Reproductive system and brest Disorders	0.22% 2/899 • Number of events 2 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	0.67% 6/892 • Number of events 6 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Congenital, familial and genetic disorders Congenital, familial and genetic Disorders	0.22% 2/899 • Number of events 2 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	0.45% 4/892 • Number of events 4 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Eye disorders Eye Disorders	0.67% 6/899 • Number of events 6 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	0.22% 2/892 • Number of events 2 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Endocrine disorders Endocrine Disorders	0.22% 2/899 • Number of events 2 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	0.11% 1/892 • Number of events 1 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.

Measure	Arm 1 n=899 participants at risk Standard glycemic control to maintain HbA1c between 8.0-9.0%. Metformin 500 mg Rosiglitazone 4 mg Glimepiride 2 mg Insulin 1 unit 9 lbs	Arm 2 n=892 participants at risk Intensive glycemic control lower HbA1c below 6.0%. Metformin 500 mg (go up to 2000 mg) Rosiglitazone 4 mg bid Glimepiride 8 mg Insulin 1 unit 9 lbs add one injection to Arm 1
Musculoskeletal and connective tissue disorders Musculoskeletal	54.8% 493/899 • Number of events 493 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	53.8% 480/892 • Number of events 480 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Infections and infestations Infections	42.8% 385/899 • Number of events 385 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	39.7% 354/892 • Number of events 354 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
General disorders General Disorders	35.0% 315/899 • Number of events 315 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	32.5% 290/892 • Number of events 290 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Nervous system disorders Nervous system	35.4% 318/899 • Number of events 318 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	31.7% 283/892 • Number of events 283 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Gastrointestinal disorders Gastrointestinal Disorders	32.0% 288/899 • Number of events 288 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	32.4% 289/892 • Number of events 289 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Injury, poisoning and procedural complications Injury	26.1% 235/899 • Number of events 235 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	25.4% 227/892 • Number of events 227 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Respiratory, thoracic and mediastinal disorders Respiratory	25.3% 227/899 • Number of events 227 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	24.4% 218/892 • Number of events 218 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Skin and subcutaneous tissue disorders Skin	23.8% 214/899 • Number of events 214 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	23.1% 206/892 • Number of events 206 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Investigations Investigations	18.6% 167/899 • Number of events 167 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	19.5% 174/892 • Number of events 174 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Eye disorders Eye Disorders	20.6% 185/899 • Number of events 185 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	20.5% 183/892 • Number of events 183 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Psychiatric disorders Psychiatric	19.5% 175/899 • Number of events 175 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	18.6% 166/892 • Number of events 166 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Renal and urinary disorders Renal	15.4% 138/899 • Number of events 138 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	17.7% 158/892 • Number of events 158 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Metabolism and nutrition disorders Metabolism	12.8% 115/899 • Number of events 115 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	14.8% 132/892 • Number of events 132 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Vascular disorders Vascular	12.8% 115/899 • Number of events 115 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	10.1% 90/892 • Number of events 90 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Surgical and medical procedures Surgical	8.6% 77/899 • Number of events 77 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	10.0% 89/892 • Number of events 89 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Cardiac disorders Cardiac Disorders	7.7% 69/899 • Number of events 69 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	7.0% 62/892 • Number of events 62 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms	8.7% 78/899 • Number of events 78 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	7.2% 64/892 • Number of events 64 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Blood and lymphatic system disorders Blood	7.5% 67/899 • Number of events 67 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	9.8% 87/892 • Number of events 87 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Reproductive system and breast disorders Reproductive	9.1% 82/899 • Number of events 82 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	7.0% 62/892 • Number of events 62 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Immune system disorders Immune	7.5% 67/899 • Number of events 67 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	6.5% 58/892 • Number of events 58 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.
Ear and labyrinth disorders Ear	6.8% 61/899 • Number of events 61 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.	5.8% 52/892 • Number of events 52 • The adverse events were collected in a 82-month period. Adverse events were reported by staff at visits or the patient between visits. Staff submitted an Adverse event report, using the FDA Form 3500, for each patient with a severe or unexpected reaction that may reasonably be treatment-related. Reports were screened by the research pharmacist and Study Co-Chairs.