Trial Outcomes & Findings for Drug-Eluting Bead, Irinotecan Therapy for Unresectable Intrahepatic Cholangiocarcinoma w/Concomitant Gemcitabine and Cisplatin or Carboplatin (NCT NCT01648023)

Last Updated: 2025-02-27

Results Overview

Tumor response will be determined using Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Response will be classified as: Complete Response - disappearance of all lesions; Partial Response - at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter or 30% reduction in arterial enhancement; Progressive Disease - at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest longest diameter recorded since start of treatment or appearance of one or more new lesions greater than 1cm in size; Stable Disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since start of treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

Assessed at 2, 4 and 6 months. 6 months reported.

Results posted on

2025-02-27

Participant Flow

Participant milestones

Participant milestones
Measure	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
Overall Study STARTED	25	24
Overall Study COMPLETED	24	22
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
Overall Study Screen Fail Post Randomization	1	2

Baseline Characteristics

Drug-Eluting Bead, Irinotecan Therapy for Unresectable Intrahepatic Cholangiocarcinoma w/Concomitant Gemcitabine and Cisplatin or Carboplatin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo n=24 Participants Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo n=22 Participants Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo	Total n=46 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	15 Participants n=99 Participants	13 Participants n=107 Participants	28 Participants n=206 Participants
Age, Categorical >=65 years	9 Participants n=99 Participants	9 Participants n=107 Participants	18 Participants n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	13 Participants n=107 Participants	26 Participants n=206 Participants
Sex: Female, Male Male	11 Participants n=99 Participants	9 Participants n=107 Participants	20 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	3 Participants n=107 Participants	5 Participants n=206 Participants
Race (NIH/OMB) White	21 Participants n=99 Participants	19 Participants n=107 Participants	40 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: Assessed at 2, 4 and 6 months. 6 months reported.

Outcome measures

Outcome measures
Measure	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo n=24 Participants Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo n=22 Participants Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
Tumor Response (Overall Response = Complete Response + Partial Response + Progressive Disease + Stable Disease)	24 participants	22 participants

SECONDARY outcome

Timeframe: 4.5 Years

Population: All randomized subjects who receive at least one cycle of intravenous chemotherapy or LC or ONCOZENE beads loaded with irinotecan. Subjects will be grouped according to their randomization.

Long-term follow-up will occur every 3-4 months for up to one year after discontinuation of active study treatment. Subjects who have completed the long-term follow-up period will be monitored every 3 - 6 months until evidence of progression of disease. Once there is progression of disease subjects will be followed for overall survival by telephone or standard physician follow-ups as per standard of care until death.

Outcome measures

Outcome measures
Measure	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo n=24 Participants Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo n=22 Participants Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
Overall Survival	33.7 Months Interval 13.5 to 54.5	12.6 Months Interval 8.7 to 33.4

Adverse Events

Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo

Serious events: 21 serious events

Other events: 24 other events

Deaths: 17 deaths

Randomization to Gem-Cis or Gem-Carbo

Serious events: 19 serious events

Other events: 19 other events

Deaths: 16 deaths

Serious adverse events

Other adverse events

Additional Information

Robert Martin, MD, PhD

University of Louisville

Phone: 502-629-3355

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo n=24 participants at risk Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo n=22 participants at risk Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
Blood and lymphatic system disorders Neutropenia	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Blood and lymphatic system disorders Neutropenic Fever	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Infections and infestations Neutropenic Sepsis	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Oversedation	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Pain	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Musculoskeletal and connective tissue disorders Pelvic Fracture	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Infections and infestations Pneumonia	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Infections and infestations Sepsis	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Vascular disorders Stroke	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Subarachnoid Hemorrhage	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Hepatobiliary disorders Subcapsular Liver Abscess	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Systemic Inflammatory Response Syndrome	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Blood and lymphatic system disorders Thrombocytopenia	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Vascular disorders TIA	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Upper GI Hemorrhage	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Vomiting	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Infections and infestations Wound Infection	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Hepatobiliary disorders Biliary Strictures	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Hepatobiliary disorders Biliary Tract Infection	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Cardiac disorders Congestive Heart Failure	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Dehydration	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Diarrhea	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Enterocutaneous Fistula	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Infections and infestations ESBL E Coli Bacteremia	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Infections and infestations ESBL E Coli Urinary Tract Infection	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Fatigue	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Fever	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Investigations Hypercalcemia	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Cardiac disorders Hypertension	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Investigations Hypoglycemia	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Ischemic Colitis	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Lethargy	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Blood and lymphatic system disorders Leukocytosis	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Hepatobiliary disorders Liver Abscess	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Hepatobiliary disorders Liver Failure	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Cardiac disorders Myocardial Infarction	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Abdominal Pain	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Cardiac disorders Acute Cardiac Injury	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)

Other adverse events
Measure	Randomization to LC OR ONCOZENE Bead With Gem-Cis or Gem-Carbo n=24 participants at risk Transarterial Chemoembolization (LC or ONCOZENE Bead) with Gem-Cis or Gem-Carbo LC or ONCOZENE Bead with Gem-Cis or Gem-Carbo	Randomization to Gem-Cis or Gem-Carbo n=22 participants at risk Gem-Cis or Gem-Carbo alone Gem-Cis or Gem-Carbo
General disorders Weakness	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	13.6% 3/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders weight Loss	25.0% 6/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Tremors	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Abdominal Distension	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Abdominal Pain	87.5% 21/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	22.7% 5/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Immune system disorders Gout	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Agitation	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Aguesia	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Immune system disorders Alopecia	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Blood and lymphatic system disorders Anemia	50.0% 12/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	40.9% 9/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Anorexia	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Psychiatric disorders Anxiety	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Musculoskeletal and connective tissue disorders Arthralgia	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Hepatobiliary disorders Ascites	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Musculoskeletal and connective tissue disorders Back Pain	16.7% 4/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	18.2% 4/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Balance Problems	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Edema	29.2% 7/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	27.3% 6/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Musculoskeletal and connective tissue disorders Body Aches	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Bone Pain	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Blood and lymphatic system disorders Bruising	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Infections and infestations C Difficile	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Infections and infestations Cellulitis	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Cachexia	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Chills	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Hepatobiliary disorders Cholecystitis	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Hepatobiliary disorders Cholangitis	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Cold Sensitivity	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Blood and lymphatic system disorders Coagulopathy	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Psychiatric disorders Confusion	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Gastrointestinal disorders Constipation	70.8% 17/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	27.3% 6/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Respiratory, thoracic and mediastinal disorders Cough	16.7% 4/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Decreased Appetite	20.8% 5/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	13.6% 3/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Dysgeusia	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	31.8% 7/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Skin and subcutaneous tissue disorders Decubitus Ulcer	0.00% 0/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Blood and lymphatic system disorders Thrombosis	12.5% 3/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	9.1% 2/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
General disorders Dehydration	16.7% 4/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	18.2% 4/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Psychiatric disorders Delirium	8.3% 2/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	0.00% 0/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Psychiatric disorders Depression	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)
Skin and subcutaneous tissue disorders Dermatitis	4.2% 1/24 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)	4.5% 1/22 • Adverse and Serious Adverse Events were assessed for 15 months. All-Cause Morality was assessed from randomization to Date of Death from Any Cause (up to 55 months)