Trial Outcomes & Findings for Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085) (NCT NCT00759109)

Last Updated: 2017-04-07

Results Overview

Participants were tested for focal lesions by liver ultrasound and for AFP levels every 6 months the during study (treatment and follow-up). The development of hepatocellular carcinoma was determined by: 1. the appearance of a focal lesion detected by liver ultrasound with metastases confirmed by fine needle biopsy, or 2. the appearance of a focal lesion detected by ultrasound + alphafetoprotein (AFP) levels in blood \>400 ng/mL.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

150 participants

Primary outcome timeframe

During 3 years of treatment and 2 years of follow-up

Results posted on

2017-04-07

Participant Flow

The Intent-to-Treat (ITT) population included all randomized participants who took at least one dose of medication, and presented at least one further efficacy evaluation. No efficacy assessment post-baseline was obtained for 4 participants in the control group, therefore the ITT population included 146 (74 PegIntron + 72 Control) participants.

Participant milestones

Participant milestones
Measure	Arm A - PegIntron Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control Participants randomized to Arm B were under observation and received no treatment.
Overall Study STARTED	74	76
Overall Study COMPLETED	35	41
Overall Study NOT COMPLETED	39	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A - PegIntron Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control Participants randomized to Arm B were under observation and received no treatment.
Overall Study Adverse Event	17	12
Overall Study Inability to comply	1	1
Overall Study Withdrawal by Subject	9	5
Overall Study Death	4	3
Overall Study Lost to Follow-up	4	6
Overall Study Started new therapy	2	6
Overall Study HCV RNA negative	1	0
Overall Study Participant moved to a different city	0	1
Overall Study Participant had a liver transplant	0	1
Overall Study Lost during study	1	0

Baseline Characteristics

Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A - PegIntron n=74 Participants Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control n=72 Participants Participants randomized to Arm B were under observation and received no treatment.	Total n=146 Participants Total of all reporting groups
Age, Continuous	57 Years STANDARD_DEVIATION 8.7 • n=99 Participants	59.7 Years STANDARD_DEVIATION 7.2 • n=107 Participants	58.3 Years STANDARD_DEVIATION 8.1 • n=206 Participants
Sex: Female, Male Female	22 Participants n=99 Participants	34 Participants n=107 Participants	56 Participants n=206 Participants
Sex: Female, Male Male	52 Participants n=99 Participants	38 Participants n=107 Participants	90 Participants n=206 Participants

PRIMARY outcome

Timeframe: During 3 years of treatment and 2 years of follow-up

Population: ITT population

Outcome measures

Outcome measures
Measure	Arm A - PegIntron n=74 Participants Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control n=72 Participants Participants randomized to Arm B were under observation and received no treatment.
Number of Participants With the Development of Hepatocellular Carcinoma (HCC)	15 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline, During 3 years of treatment and 2 years of follow-up

Population: ITT population

The development of hepatic decompensation, defined as worsening of the hepatic function as measured by Child Pugh Score. The Child Pugh score was calculated based on biochemical changes (changes in serum albumin, serum bilirubin, prothrombin time) and clinical impairment (ascites, encephalopathies) or both. Each of the 5 parameters was scored from 1-3, and the Child Pugh Score represented the total score. The maximum score was 15, and a score of 10-15 represents the worst outcome and a life expectancy of 1-3 years.

Outcome measures

Outcome measures
Measure	Arm A - PegIntron n=74 Participants Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control n=72 Participants Participants randomized to Arm B were under observation and received no treatment.
Number of Participants With Development of Hepatic Decompensation	4 Participants	9 Participants

SECONDARY outcome

Timeframe: During 3 years of treatment and 2 years of follow-up

Population: ITT population

Survival time was defined as time from screening visit to the death of the participant and was studied with Kaplan-Meier and Log-rank tests. If a participant did not die, he or she was censored with the last available date.

Outcome measures

Outcome measures
Measure	Arm A - PegIntron n=74 Participants Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control n=72 Participants Participants randomized to Arm B were under observation and received no treatment.
Survival Time of Participants	5.2840 Years Interval 3.0116 to 5.2841	4.0602 Years The median confidence interval for control group could not be calculated due to the low number of events, however, the median survival time for the control group was estimated to be higher than 4.0602 years.

SECONDARY outcome

Timeframe: Baseline and every year during 3 years of treatment

Population: ITT population

Virological Response rate was measured by the disappearance of Hepatitis C Virus from serum. Serum samples from participants were analyzed for the presence of HCV-RNA using a qualitative polymerase chain reaction (PCR).

Outcome measures

Outcome measures
Measure	Arm A - PegIntron n=74 Participants Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control n=72 Participants Participants randomized to Arm B were under observation and received no treatment.
Number of Patients With a Virological Response Rate 1 year	3 Participants	0 Participants
Number of Patients With a Virological Response Rate Baseline	0 Participants	0 Participants
Number of Patients With a Virological Response Rate 2 years	1 Participants	0 Participants
Number of Patients With a Virological Response Rate 3 years	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and at 18 months of treatment

Population: Participants with tissue biopsies at 18 months.

PCNA-LI was measured at baseline and at 18 months of treatment, and the change in PCNA-LI was calculated. To measure PCNA-LI, liver tissue samples obtained from biopsies were fixed and immunostained to detect PCNA. PCNA-LI is the percentage of immunohistochemically stained (PCNA positive) cells in 1,000 HCC cells counted. A higher PCNA-LI indicates a worse outcome.

Outcome measures

Outcome measures
Measure	Arm A - PegIntron n=37 Participants Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control n=26 Participants Participants randomized to Arm B were under observation and received no treatment.
Change in the Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI)	-2.0 Score on a scale Standard Deviation 3.2	-0.9 Score on a scale Standard Deviation 2.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: ITT population

Liver tissues obtained from biopsies were fixed and immunostained to detect PCNA. PCNA-LI is the percentage of immunohistochemically stained (PCNA positive) cells in 1,000 HCC cells counted. A higher PCNA-LI indicates a worse outcome.

Outcome measures

Outcome measures
Measure	Arm A - PegIntron n=74 Participants Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control n=72 Participants Participants randomized to Arm B were under observation and received no treatment.
Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI) at Baseline	4.2 Score on a scale Standard Deviation 2.1	3.9 Score on a scale Standard Deviation 1.6

Adverse Events

Arm A - PegIntron

Serious events: 36 serious events

Other events: 55 other events

Deaths: 0 deaths

Arm B - Control

Serious events: 30 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President,Global Clinical Development

Merck Sharp and Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restriction on the principal investigator (PI) is that the PI agrees not to publish or publicly present any results of the study without the prior written permission of the sponsor. The PI further agrees to allow the sponsor to review, 30 days prior to submission for publication or presentation, copies of abstracts or manuscripts for publication (including texts of oral presentations) which report any results of the study.
Publication restrictions are in place

Restriction type: OTHER

Measure	Arm A - PegIntron n=74 participants at risk Participants randomized to Arm A received peginterferon α-2b, 50 μg, weekly, for a period of 3 years.	Arm B - Control n=76 participants at risk Participants randomized to Arm B were under observation and received no treatment.
Blood and lymphatic system disorders ANAEMIA	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Blood and lymphatic system disorders THROMBOCYTOPENIA	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	1.4% 1/74 • Number of events 2 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Cardiac disorders ATRIAL FIBRILLATION	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Cardiac disorders CONGESTIVE CARDIOMYOPATHY	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Cardiac disorders PERICARDIAL EFFUSION	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Cardiac disorders VENTRICULAR TACHYCARDIA	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders ASCITES	2.7% 2/74 • Number of events 2 A total of 15 serious adverse events resulted in death.	2.6% 2/76 • Number of events 2 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders DIARRHOEA	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders GASTRIC DYSPLASIA	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders HAEMATEMESIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders INGUINAL HERNIA	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders INTESTINAL ISCHAEMIA	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders MELAENA	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders OESOPHAGEAL VARICES HAEMORRHAGE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders VARICES OESOPHAGEAL	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Gastrointestinal disorders VOMITING	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
General disorders DEATH	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
General disorders HYPERPYREXIA	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
General disorders PYREXIA	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 2 A total of 15 serious adverse events resulted in death.
Hepatobiliary disorders BILIARY DILATATION	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Hepatobiliary disorders CHOLECYSTITIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Hepatobiliary disorders CHOLELITHIASIS	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Hepatobiliary disorders HEPATIC FAILURE	2.7% 2/74 • Number of events 2 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Hepatobiliary disorders HEPATORENAL SYNDROME	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Hepatobiliary disorders PORTAL VEIN THROMBOSIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Immune system disorders CRYOGLOBULINAEMIA	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Infections and infestations BRONCHITIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Infections and infestations BRONCHOPNEUMONIA	1.4% 1/74 • Number of events 2 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Infections and infestations CYSTITIS	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Infections and infestations MUSCLE ABSCESS	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Infections and infestations PERITONITIS BACTERIAL	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Infections and infestations SALMONELLOSIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Injury, poisoning and procedural complications CLAVICLE FRACTURE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Injury, poisoning and procedural complications FEMUR FRACTURE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Injury, poisoning and procedural complications HAND FRACTURE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Injury, poisoning and procedural complications HUMERUS FRACTURE	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Injury, poisoning and procedural complications LOWER LIMB FRACTURE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Injury, poisoning and procedural complications RIB FRACTURE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Injury, poisoning and procedural complications THORACIC VERTEBRAL FRACTURE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	2.6% 2/76 • Number of events 2 A total of 15 serious adverse events resulted in death.
Injury, poisoning and procedural complications UPPER LIMB FRACTURE	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Investigations ULTRASOUND LIVER ABNORMAL	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Metabolism and nutrition disorders HYPOALBUMINAEMIA	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BREAST CANCER	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	2.6% 2/76 • Number of events 2 A total of 15 serious adverse events resulted in death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) GASTRIC CANCER	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) HEPATIC NEOPLASM MALIGNANT	20.3% 15/74 • Number of events 15 A total of 15 serious adverse events resulted in death.	14.5% 11/76 • Number of events 11 A total of 15 serious adverse events resulted in death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LYMPHOMA	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PANCREATIC NEOPLASM	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Nervous system disorders BRAIN MASS	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Nervous system disorders CEREBRAL HAEMORRHAGE	5.4% 4/74 • Number of events 4 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Nervous system disorders COMA HEPATIC	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Nervous system disorders EPILEPSY	2.7% 2/74 • Number of events 2 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Nervous system disorders HAEMORRHAGE INTRACRANIAL	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Nervous system disorders NORMAL PRESSURE HYDROCEPHALUS	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Nervous system disorders QUADRIPLEGIA	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Nervous system disorders SYNCOPE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Renal and urinary disorders ANURIA	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Renal and urinary disorders GLOMERULONEPHRITIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Renal and urinary disorders NEPHROTIC SYNDROME	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Reproductive system and breast disorders BREAST PAIN	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY FAILURE	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Respiratory, thoracic and mediastinal disorders EPISTAXIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Respiratory, thoracic and mediastinal disorders VOCAL CORD POLYP	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Skin and subcutaneous tissue disorders HYPERHIDROSIS	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Skin and subcutaneous tissue disorders PSORIASIS	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Skin and subcutaneous tissue disorders RASH	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Surgical and medical procedures COLON POLYPECTOMY	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Surgical and medical procedures GASTRECTOMY	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Surgical and medical procedures INGUINAL HERNIA REPAIR	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Surgical and medical procedures KNEE ARTHROPLASTY	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Vascular disorders BLEEDING VARICOSE VEIN	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.
Vascular disorders HYPERTENSIVE CRISIS	1.4% 1/74 • Number of events 1 A total of 15 serious adverse events resulted in death.	0.00% 0/76 A total of 15 serious adverse events resulted in death.
Vascular disorders SYSTOLIC HYPERTENSION	0.00% 0/74 A total of 15 serious adverse events resulted in death.	1.3% 1/76 • Number of events 1 A total of 15 serious adverse events resulted in death.