Trial Outcomes & Findings for A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia (NCT NCT00357682)

Last Updated: 2025-05-01

Results Overview

Death is recorded on a continuous basis through reporting from trial sites. Oesophageal adenocarcinoma is recorded through endoscopies taken every two years or ad-hoc at clinician decision High Grade Dysplasia is recorded through endoscopies taken every two years or ad-hoc at clinician decision

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2557 participants

Primary outcome timeframe

Events are assessed from the date of randomisation to the end of study which can be patient withdrawal, loss to follow up or study end (8 years or 10 years from randomisation, depending on consent)

Results posted on

2025-05-01

Participant Flow

2557 eligible participants were recruited across from 4th March 2005 to 25th February 2009. There were 84 centres across England, Scotland, Wales, and Northern Ireland, and one in McMaster Health Sciences Centre, Hamilton, ON, Canada.

Participant milestones

Participant milestones
Measure	Arm A 20mg Esomeprazole Esomeprazole: 20mg per day	Arm B 80mg Esomeprazole Esomeprazole: 80mg per day	Arm C 20mg Esomeprazole + 300mg Aspirin Esomeprazole: 20mg per day Aspirin: 300mg per day	Arm D 80mg Esomeprazole + 300mg Aspirin Esomeprazole: 80mg per day Aspirin: 300mg per day
Overall Study STARTED	705	704	571	577
Overall Study COMPLETED	364	394	320	312
Overall Study NOT COMPLETED	341	310	251	265

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A 20mg Esomeprazole Esomeprazole: 20mg per day	Arm B 80mg Esomeprazole Esomeprazole: 80mg per day	Arm C 20mg Esomeprazole + 300mg Aspirin Esomeprazole: 20mg per day Aspirin: 300mg per day	Arm D 80mg Esomeprazole + 300mg Aspirin Esomeprazole: 80mg per day Aspirin: 300mg per day
Overall Study Did not receive allocated Treatment	10	9	9	10
Overall Study Withdrew consent	6	6	5	5
Overall Study Lost to Follow-up	39	33	26	35
Overall Study Adverse Event	24	32	22	27
Overall Study Physician Decision	32	20	24	30
Overall Study Patient decision	73	80	51	59
Overall Study Other reason	157	130	114	99

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A n=699 Participants 20mg Esomeprazole Esomeprazole: 20mg per day	Arm B n=698 Participants 80mg Esomeprazole Esomeprazole: 80mg per day	Arm C n=566 Participants 20mg Esomeprazole + 300mg Aspirin Esomeprazole: 20mg per day Aspirin: 300mg per day	Arm D n=572 Participants 80mg Esomeprazole + 300mg Aspirin Esomeprazole: 80mg per day Aspirin: 300mg per day	Total n=2535 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=699 Participants	0 Participants n=698 Participants	0 Participants n=566 Participants	0 Participants n=572 Participants	0 Participants n=2535 Participants
Age, Categorical Between 18 and 65 years	495 Participants n=699 Participants	494 Participants n=698 Participants	429 Participants n=566 Participants	418 Participants n=572 Participants	1836 Participants n=2535 Participants
Age, Categorical >=65 years	204 Participants n=699 Participants	204 Participants n=698 Participants	137 Participants n=566 Participants	154 Participants n=572 Participants	699 Participants n=2535 Participants
Sex: Female, Male Female	135 Participants n=699 Participants	136 Participants n=698 Participants	118 Participants n=566 Participants	124 Participants n=572 Participants	513 Participants n=2535 Participants
Sex: Female, Male Male	564 Participants n=699 Participants	562 Participants n=698 Participants	448 Participants n=566 Participants	448 Participants n=572 Participants	2022 Participants n=2535 Participants
Race and Ethnicity Not Collected	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: Events are assessed from the date of randomisation to the end of study which can be patient withdrawal, loss to follow up or study end (8 years or 10 years from randomisation, depending on consent)

Population: Intent to treat population

Outcome measures

Outcome measures
Measure	Aspirin n=1138 Participants Subjects randomised to receive 300mg daily aspirin	No Aspirin n=1142 Participants Subjects randomised to receive no aspirin	Low Dose PPI n=1265 Participants Subjects randomised to receive 20mg daily PPI	High Dose PPI n=1270 Participants Subjects randomised to receive 80mg daily PPI
First Event of Death, Oesophageal Adenocarcinoma, High Grade Dysplasia	127 Participants	154 Participants	174 Participants	139 Participants

SECONDARY outcome

Timeframe: Through study completion, an average of 8.9 years.

Population: Intent to treat population

Accelerated Failure Time (AFT) analysis comparing time to all cause mortality in low dose PPI (20mg) patients to high dose PPI (80mg) patients and in aspirin patients to non-aspirin patients. Included in AFT model are stratification factors (Barrett's length, age group and presence of baseline intestinal metaplasia) and aspirin randomisation group.

Outcome measures

Outcome measures
Measure	Aspirin n=1138 Participants Subjects randomised to receive 300mg daily aspirin	No Aspirin n=1142 Participants Subjects randomised to receive no aspirin	Low Dose PPI n=1265 Participants Subjects randomised to receive 20mg daily PPI	High Dose PPI n=1270 Participants Subjects randomised to receive 80mg daily PPI
All Cause Mortality	73 Participants	90 Participants	105 Participants	79 Participants

SECONDARY outcome

Timeframe: Assessed every 2 years through study completion, an average of 8.9 years

Number of aspirin and non-aspirin patients and low dose PPI and high dose PPI patients with adenocarcinoma oesophageal cancer

Outcome measures

Outcome measures
Measure	Aspirin n=1138 Participants Subjects randomised to receive 300mg daily aspirin	No Aspirin n=1142 Participants Subjects randomised to receive no aspirin	Low Dose PPI n=1265 Participants Subjects randomised to receive 20mg daily PPI	High Dose PPI n=1270 Participants Subjects randomised to receive 80mg daily PPI
Adenocarcinoma Oesophageal Cancer	35 Participants	35 Participants	41 Participants	40 Participants

SECONDARY outcome

Timeframe: High Grade Dysplasia is assessed every two years through study completion, an average of 8.9 years.

Diagnosis of high grade dysplasia is compared in aspirin and non-aspirin trial patients, and in high dose PPI and low dose PPI patients.

Outcome measures

Outcome measures
Measure	Aspirin n=1138 Participants Subjects randomised to receive 300mg daily aspirin	No Aspirin n=1142 Participants Subjects randomised to receive no aspirin	Low Dose PPI n=1265 Participants Subjects randomised to receive 20mg daily PPI	High Dose PPI n=1270 Participants Subjects randomised to receive 80mg daily PPI
High Grade Dysplasia	37 Participants	55 Participants	59 Participants	44 Participants

Adverse Events

Aspirin

Serious events: 340 serious events

Other events: 0 other events

Deaths: 73 deaths

No Aspirin

Serious events: 378 serious events

Other events: 0 other events

Deaths: 90 deaths

Low Dose PPI

Serious events: 359 serious events

Other events: 0 other events

Deaths: 105 deaths

High Dose PPI

Serious events: 359 serious events

Other events: 0 other events

Deaths: 79 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Prof Janusz A Z Jankowski

NICE

Phone: 07968 479355

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Aspirin n=1138 participants at risk Subjects randomised to receive 300mg daily aspirin	No Aspirin n=1142 participants at risk Subjects randomised to receive no aspirin	Low Dose PPI n=1265 participants at risk Subjects randomised to receive 20mg daily PPI	High Dose PPI n=1270 participants at risk Subjects randomised to receive 80mg daily PPI
Musculoskeletal and connective tissue disorders Tendon rupture	0.18% 2/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Endocrine disorders Goitre	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Endocrine disorders Hypothyroidism	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Metabolism and nutrition disorders Acidosis	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Metabolism and nutrition disorders Hyperglycemia	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.35% 4/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.16% 2/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.24% 3/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Metabolism and nutrition disorders Hyperuricemia	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Metabolism and nutrition disorders Hypokalemia	0.18% 2/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Metabolism and nutrition disorders Hypomagnesemia	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.24% 3/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Metabolism and nutrition disorders Hyponatremia	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Abdominal infection	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Anorectal infection	0.18% 2/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.16% 2/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Appendicitis	0.26% 3/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.39% 5/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Appendicitis perforated	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Biliary tract infection	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Bladder infection	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.16% 2/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Bone infection	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Device related infection	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Enterocolitis infectious	0.79% 9/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.79% 9/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.63% 8/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.79% 10/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Eye infection	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Hepatic infection	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Inner Ear Infection	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Intestinal parasite	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Joint infection	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Kidney infection	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Lung infection	2.2% 25/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	2.7% 31/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	2.2% 28/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	2.2% 28/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Pharyngitis	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Prostate infection	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Psoas abscess	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Salivary gland infection	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Scrotal infection	0.18% 2/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.24% 3/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Sepsis	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.16% 2/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Skin infection	0.62% 7/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	1.2% 14/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.71% 9/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.94% 12/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Soft tissue infection	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Tooth infection	0.18% 2/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.16% 2/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Upper respiratory infection	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.09% 1/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.08% 1/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Urinary tract infection	0.97% 11/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.35% 4/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.63% 8/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.55% 7/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Infections and infestations Wound infection	0.09% 1/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.53% 6/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.32% 4/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.24% 3/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).
Vascular disorders Hematoma	0.00% 0/1138 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.18% 2/1142 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.00% 0/1265 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).	0.16% 2/1270 • Adverse event monitoring started from the time the patient commenced study medication until 30 days after stopping trial medication (an average of 8.9 years).