Trial Outcomes & Findings for Efficacy Study of Anakinra, Pentoxifylline, and Zinc Compared to Methylprednisolone in Severe Acute Alcoholic Hepatitis (NCT NCT01809132)

NCT ID: NCT01809132

Last Updated: 2021-11-01

Results Overview

Death at 180 days

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

104 participants

Primary outcome timeframe

Time to event up to 6 months

Results posted on

2021-11-01

Participant Flow

Participant milestones

Participant milestones
Measure	Anakinra & Pentoxifylline & Zinc Sulfate anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational Individuals who choose not to participate in the interventional arm of the trial will be receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.
Overall Study STARTED	53	50	1
Overall Study COMPLETED	53	50	0
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Anakinra & Pentoxifylline & Zinc Sulfate anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational Individuals who choose not to participate in the interventional arm of the trial will be receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

The observational subject was lost to follow up.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anakinra & Pentoxifylline & Zinc Sulfate n=53 Participants anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone n=50 Participants methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational n=1 Participants Individuals who choose not to participate in the interventional arm of the trial will be receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.	Total n=104 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=53 Participants • The observational subject was lost to follow up.	0 Participants n=50 Participants • The observational subject was lost to follow up.	0 Participants The observational subject was lost to follow up.	0 Participants n=103 Participants • The observational subject was lost to follow up.
Age, Categorical Between 18 and 65 years	53 Participants n=53 Participants • The observational subject was lost to follow up.	50 Participants n=50 Participants • The observational subject was lost to follow up.	0 Participants The observational subject was lost to follow up.	103 Participants n=103 Participants • The observational subject was lost to follow up.
Age, Categorical >=65 years	0 Participants n=53 Participants • The observational subject was lost to follow up.	0 Participants n=50 Participants • The observational subject was lost to follow up.	0 Participants The observational subject was lost to follow up.	0 Participants n=103 Participants • The observational subject was lost to follow up.
Sex: Female, Male Female	18 Participants n=53 Participants	22 Participants n=50 Participants	1 Participants n=1 Participants	41 Participants n=104 Participants
Sex: Female, Male Male	35 Participants n=53 Participants	28 Participants n=50 Participants	0 Participants n=1 Participants	63 Participants n=104 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=53 Participants	9 Participants n=50 Participants	0 Participants n=1 Participants	19 Participants n=104 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=53 Participants	38 Participants n=50 Participants	1 Participants n=1 Participants	77 Participants n=104 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=53 Participants	3 Participants n=50 Participants	0 Participants n=1 Participants	8 Participants n=104 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=53 Participants	0 Participants n=50 Participants	0 Participants n=1 Participants	0 Participants n=104 Participants
Race (NIH/OMB) Asian	1 Participants n=53 Participants	0 Participants n=50 Participants	0 Participants n=1 Participants	1 Participants n=104 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=53 Participants	0 Participants n=50 Participants	0 Participants n=1 Participants	0 Participants n=104 Participants
Race (NIH/OMB) Black or African American	5 Participants n=53 Participants	3 Participants n=50 Participants	0 Participants n=1 Participants	8 Participants n=104 Participants
Race (NIH/OMB) White	47 Participants n=53 Participants	47 Participants n=50 Participants	1 Participants n=1 Participants	95 Participants n=104 Participants
Race (NIH/OMB) More than one race	0 Participants n=53 Participants	0 Participants n=50 Participants	0 Participants n=1 Participants	0 Participants n=104 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=53 Participants	0 Participants n=50 Participants	0 Participants n=1 Participants	0 Participants n=104 Participants

PRIMARY outcome

Timeframe: Time to event up to 6 months

Population: Intention to treat

Death at 180 days

Outcome measures

Outcome measures
Measure	Anakinra & Pentoxifylline & Zinc Sulfate n=53 Participants anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone n=50 Participants methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational Individuals who choose not to participate in the interventional arm of the trial will be receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.
180 Days Mortality	17 Participants	22 Participants	0 Participants

SECONDARY outcome

Timeframe: 28 days

Population: This outcome could not be calculated for the observational subject who was lost to follow up. Analysis were limited to the subjects that were alive for this time point.

Model of End Stage Liver Disease Score calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR). MELD score ranges from 6-40. A higher score indicates a lesser outcome. The Model for End Stage Liver Disease scoring system is based on the INR, total serum bilirubin and serum creatinine. The measure reflects 90 day prognosis of alcohol associated liver disease from the time of measurement and therefore can only be assessed on subjects who are alive at the specified time point since lab values from that time point are required for the measure.

Outcome measures

Outcome measures
Measure	Anakinra & Pentoxifylline & Zinc Sulfate n=30 Participants anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone n=29 Participants methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational Individuals who choose not to participate in the interventional arm of the trial will be receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.
MELD Score at 28 Days	22.57 score on a scale Standard Deviation 6.31	20.95 score on a scale Standard Deviation 6.44	—

SECONDARY outcome

Timeframe: 90 Days

Population: This outcome could not be calculated for the observational subject who was lost to follow up. Analysis were limited to the subjects that were alive for this time point.

Outcome measures

Outcome measures
Measure	Anakinra & Pentoxifylline & Zinc Sulfate n=22 Participants anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone n=17 Participants methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational Individuals who choose not to participate in the interventional arm of the trial will be receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.
MELD Score at 90 Days	15.50 score on a scale Standard Deviation 6.11	16.38 score on a scale Standard Deviation 9.58	—

SECONDARY outcome

Timeframe: 180 Days

Population: This outcome could not be calculated for the observational subject who was lost to follow up. Analysis were limited to the subjects that were alive for this time point.

Outcome measures

Outcome measures
Measure	Anakinra & Pentoxifylline & Zinc Sulfate n=19 Participants anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone n=15 Participants methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational Individuals who choose not to participate in the interventional arm of the trial will be receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.
MELD Score at 180 Days	15.81 score on a scale Standard Deviation 10.10	11.85 score on a scale Standard Deviation 4.47	—

Adverse Events

Anakinra & Pentoxifylline & Zinc Sulfate

Serious events: 33 serious events

Other events: 20 other events

Deaths: 17 deaths

Methylprednisolone

Serious events: 30 serious events

Other events: 4 other events

Deaths: 22 deaths

Observational

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Anakinra & Pentoxifylline & Zinc Sulfate n=53 participants at risk anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone n=50 participants at risk methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational Individuals who choose not to participate in the interventional arm of the trial will receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.
Gastrointestinal disorders Nausea	9.4% 5/53 • Number of events 5 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	0.00% 0/50 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Renal and urinary disorders Urinary tract infection	9.4% 5/53 • Number of events 5 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	0.00% 0/50 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Vascular disorders Hematemesis	7.5% 4/53 • Number of events 4 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	0.00% 0/50 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Hepatobiliary disorders Ascites	5.7% 3/53 • Number of events 3 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	6.0% 3/50 • Number of events 3 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations C. difficile infection	5.7% 3/53 • Number of events 3 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	2.0% 1/50 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.

Additional Information

Dr. Mack C. Mitchell

UTexas Southwestern Medical Center

Phone: 2146485036

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Anakinra & Pentoxifylline & Zinc Sulfate n=53 participants at risk anakinra 100mg subcutaneous injection daily for 14 days pentoxifylline 400 mg orally three times daily for 28 day zinc sulfate 220 mg orally for 180 days Anakinra: Anakinra, interleukin-1 receptor antagonist; 100 mg/0.67 mL solution for subcutaneous injection. Pentoxifylline: Pentoxifylline, generic Zinc Sulfate: Zinc Sulfate, nutritional supplement	Methylprednisolone n=50 participants at risk methylprednisolone 32 mg orally daily for 28 days Methylprednisolone: Methylprednisolone, corticosteroid	Observational Individuals who choose not to participate in the interventional arm of the trial will receive standard care and be observed for 6 months. They will be enrolled to have baseline and interval health information and laboratory results collected.
Renal and urinary disorders Acute Kidney Injury	18.9% 10/53 • Number of events 10 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	26.0% 13/50 • Number of events 13 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Vascular disorders Upper GI hemorrhage	7.5% 4/53 • Number of events 4 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	8.0% 4/50 • Number of events 4 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations Clostridium difficile infection	7.5% 4/53 • Number of events 4 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	4.0% 2/50 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations Aspergillus infection	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	6.0% 3/50 • Number of events 3 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations Nocardia sepsis	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	2.0% 1/50 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations Histoplasmosis infection	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	2.0% 1/50 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations Baceteremia	1.9% 1/53 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	2.0% 1/50 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations Candida infection	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	2.0% 1/50 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations Peritonitis	3.8% 2/53 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	0.00% 0/50 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Infections and infestations Viremia	1.9% 1/53 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	0.00% 0/50 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	4.0% 2/50 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	3.8% 2/53 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	6.0% 3/50 • Number of events 3 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	4.0% 2/50 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	4.0% 2/50 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Respiratory, thoracic and mediastinal disorders Lung infection	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	4.0% 2/50 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
General disorders Multiple Organ Dysfunction Syndrome (MODS)	3.8% 2/53 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	6.0% 3/50 • Number of events 3 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Hepatobiliary disorders Hepatic failure	5.7% 3/53 • Number of events 3 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	0.00% 0/50 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Hepatobiliary disorders Esophageal varices hemorrhage	3.8% 2/53 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	2.0% 1/50 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Cardiac disorders Ascites	11.3% 6/53 • Number of events 6 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	0.00% 0/50 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Cardiac disorders Cardiac failure	0.00% 0/53 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	2.0% 1/50 • Number of events 1 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Cardiac disorders Tachycardia	3.8% 2/53 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	0.00% 0/50 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.
Nervous system disorders Encephalopathy	5.7% 3/53 • Number of events 3 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	4.0% 2/50 • Number of events 2 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.	— 0/0 • 6 months The definitions of adverse events are the same as those used in clinicaltrials.gov Adverse events were not collected for the observational arm.