Trial Outcomes & Findings for Remote Ischemic Conditioning (RIC) in Recipients of Brain Death Donor Livers - A Feasibility and Safety Study (NCT NCT02635347)

NCT ID: NCT02635347

Last Updated: 2019-08-20

Results Overview

Proportion of enrolled liver recipients that complete all 6 remote ischemic conditioning (RIC) interventions.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 31 participants
• Primary outcome timeframe: Pre-op - Post-op day 4
• Results posted on: 2019-08-20

Participant Flow

The number of participants, 94, reflects the enrolled subjects, 31 + historical controls, 63.

Participant milestones

Measure	Remote Ischemic Conditioning (RIC) Group Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort Matched historical controls
Overall Study STARTED	51	70
Overall Study Screening	51	70
Overall Study Enrollment	31	63
Overall Study Protocol Completion	22	63
Overall Study Follow up	31	63
Overall Study Analyses	30	63
Overall Study COMPLETED	31	63
Overall Study NOT COMPLETED	20	7

Reasons for withdrawal

Measure	Remote Ischemic Conditioning (RIC) Group Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort Matched historical controls
Overall Study Failed screening	20	7

Baseline Characteristics

Remote Ischemic Conditioning (RIC) in Recipients of Brain Death Donor Livers - A Feasibility and Safety Study

Baseline characteristics by cohort

Measure	Remote Ischemic Conditioning (RIC) Cohort n=31 Participants Subjects received remote ischemic conditioning	Historical Control Cohort n=63 Participants Historical control subjects received liver transplants in an earlier period	Total n=94 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants	56 Participants n=7 Participants	82 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Age, Continuous	55.0 years n=5 Participants	56.0 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	26 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	37 Participants n=7 Participants	62 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	34 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment United States	31 Participants n=5 Participants	63 Participants n=7 Participants	94 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-op - Post-op day 4

Population: Participants enrolled to receive RIC during transplant and the initial four post-transplant days and who receive all 6 RIC interventions.Subjects in historical control cohort chosen as described above

Proportion of enrolled liver recipients that complete all 6 remote ischemic conditioning (RIC) interventions.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=31 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Percentage of Participants Completing Entire Intervention Protocol	70.96 percentage of participants Interval 54.04 to 87.89	—

SECONDARY outcome

Timeframe: Post-op days 1-4

Population: Unintubated subjects were asked to rate intervention-related pain on a scale from 0-10 for each of the postoperative interventions. The maximum pain score obtained from each subject was recorded and the median score for all subjects was calculated. Scale range from 0 - 10 with 10 indicating highest sensation of pain.

Median intervention-related pain score during each of the post-operative interventions, in extubated patients who are able to communicate. Using the Numerical Rating Scale (NRS, Ferrieira-Valente MA PAIN Volume 152, 2011), patients were asked to rate their pain following the intervention on a scale of 0-10 with 0 being no pain experienced to 10 as the maximum pain felt.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=23 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Intervention-related Pain Score	5 scores on a scale Interval 0.0 to 9.0	—

SECONDARY outcome

Timeframe: Pre-op - Post-op day 7

Population: Participants who withdrew consent due to pain from RIC intervention.

• Withdrawal of consent due to discomfort/pain in the lower extremity

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=31 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Withdrawal of Consent Due to Pain	6 participants	0 participants

SECONDARY outcome

Timeframe: Post-op days 0-7

Population: Denominator for this and other postoperative outcomes except death and complications was 30 due to the exclusion of subject who died prior to transplantation

Percentage of participants who developed Early Allograft Dysfunction (EAD) which is defined as:

• Aspartate Transaminase (AST) or Alanine Transaminase (ALT)> 2,000 U/L at any point within the first seven post-transplant days, or
• Total Bilirubin (TB) > 10 mg/dL on postoperative day 7,or
• International Normalized Ratio (INR)> 1.6 on postoperative day 7.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=30 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Percentage of Participants Who Developed Early Allograft Dysfunction (EAD)	23.3 percentage of participants	39.68 percentage of participants

SECONDARY outcome

Timeframe: Post-op days 0-7

Population: Denominator for this and other postoperative outcomes except death and complications was 30 due to the exclusion of subject who died prior to transplantation

Percentage of Participants who developed Prolonged Respiratory Insufficiency (PRI) defined as:

• Ventilator support for >2 postoperative days after transplant, or
• Reintubation after extubation, within 7 days of transplant. Patients who require brief re-intubation for an endoscopic, radiologic, or surgical procedure would not be considered to have PRI if they are extubated within 2 days of the end of the procedure.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=30 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Percentage of Participants Who Developed Prolonged Respiratory Insufficiency (PRI)	33.3 percentage of participants	28.57 percentage of participants

SECONDARY outcome

Timeframe: Post-op days 0-7

Population: Denominator for this and other postoperative outcomes except death and complications was 30 due to the exclusion of subject who died prior to transplantation

Percentage of participants who developed Acute Kidney Injury (AKI)

Based on Kidney Disease - Improving Global Outcomes (KDIGO) criteria, AKI criteria are:

Stage 2:

• 2.0-2.9 fold rise in serum creatinine from baseline

Stage 3:

• > 3.0 fold rise in serum creatinine from baseline, or
• Serum creatinine of > 4.0 mg/dL, with an acute (<48 hours) increase of 0.3 mg/dL in serum creatinine or subacute (< 7 days) increase in serum creatinine of 0.5 mg/dL, or
• Initiation of renal replacement therapy.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=30 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Percentage of Participants Who Developed Acute Kidney Injury (AKI) Stages 2 or 3	20.0 percentage of participants	25.86 percentage of participants

SECONDARY outcome

Timeframe: Post-op days 0-90

Population: Time to discontinuation of dialysis

In patients who are receiving dialysis pre-op, time to discontinuation of dialysis, if occurring within 90 days of transplantation.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=1 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=4 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Time to Dialysis Discontinuation	2 days Interval 2.0 to 2.0	15.5 days Interval 10.25 to 19.0

SECONDARY outcome

Timeframe: Post-op days 0-30

Percentage of patients with Clavien-Dindo >/= grade III b complications (Dindo D, Demartines N, Clavien P, Annals of Surgery 2004).

The Clavien-Dindo Complications grade ranges from Grade I (Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics and electrolytes and physiotherapy. This grade also includes wound infections opened at the bedside) to Grade V (Death). Grade IIIb would be any intervention requiring general anesthesia.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=30 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Presence of Clavien-Dindo Grade IIIb or Higher Complications	51.1 percentage of participants	47.62 percentage of participants

SECONDARY outcome

Timeframe: Post-op days 0-30

In patients with Clavien-Dindo >/= IIIb complications, number of such complications per patient.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=31 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Clavien-Dindo Grade IIIb or Higher - Number of Complications	1 Complications Interval 0.0 to 3.0	0 Complications Interval 0.0 to 2.0

SECONDARY outcome

Timeframe: Post-op days 0 up to 90 days

Population: Denominator for this and other postoperative outcomes except death and complications was 30 due to the exclusion of subject who died prior to transplantation

Number of days in ICU post-transplant. Starting at post-op day 0 and ending on the calendar date that the patient is transferred out of ICU, dies, or post-op day 90, whichever is soonest.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=30 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Intensive Care Unit (ICU) Length of Stay (LOS)	3.5 days Interval 2.0 to 8.0	4 days Interval 3.0 to 6.0

SECONDARY outcome

Timeframe: Post-op days 0 up to 90 days

Number of days in hospital post-transplant. Starting at post-op day 0 and ending on the calendar date that the patient is leaves the hospital, dies, or post-op day 90, whichever is soonest.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=30 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Hospital LOS	13 days Interval 8.0 to 33.0	10 days Interval 7.0 to 15.0

SECONDARY outcome

Timeframe: Post-op day 90

Population: Denominator for this and other postoperative outcomes except death and complications was 30 due to the exclusion of subject who died prior to transplantation

Percentage of patients with functioning allograft at 90 days post-transplant

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=30 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Liver Allograft Survival	90 percentage of participants	98.41 percentage of participants

SECONDARY outcome

Timeframe: Post-op day 90

Percentage of patients alive at 90 days post-transplant

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=31 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 Participants Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Patient Survival	90.32 percentage of participants	98.41 percentage of participants

SECONDARY outcome

Timeframe: Pre-op - Post-op day 4

Population: Number of subjects who completed \< 6 interventions

Number of subjects that received fewer than 6 interventions,.

Outcome measures

Measure	Remote Ischemic Conditioning (RIC) Group n=31 Participants Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Number of Subjects Not Completing Intervention Protocol	9 participants	—

Adverse Events

Remote Ischemic Conditioning (RIC) Group

Serious events: 1 serious events

Other events: 6 other events

Deaths: 3 deaths

Historical Control Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Remote Ischemic Conditioning (RIC) Group n=31 participants at risk Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 participants at risk Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Hepatobiliary disorders Primary Non-Function of liver	3.2% 1/31 • Number of events 1 • Adverse events will be tracked for the first 30 days post-transplant. In addition to the clinical.trials. gov definitions, adverse events will be monitored related to the RIC intervention: Withdrawal of consent due to discomfort/pain in the lower extremity. Any other adverse event considered by the primary clinical team to be related to the RIC intervention.	0.00% 0/63 • Adverse events will be tracked for the first 30 days post-transplant. In addition to the clinical.trials. gov definitions, adverse events will be monitored related to the RIC intervention: Withdrawal of consent due to discomfort/pain in the lower extremity. Any other adverse event considered by the primary clinical team to be related to the RIC intervention.

Other adverse events

Measure	Remote Ischemic Conditioning (RIC) Group n=31 participants at risk Participants will receive RIC during transplant and the initial four post-transplant days. During transplant: first intervention after induction of anesthesia but before commencing surgery and the second at the conclusion of the procedure. After transplant: RIC applied daily during the first four consecutive postoperative days. Pneumatic tourniquet will be used to induce RIC Remote Ischemic Conditioning (RIC): Each RIC intervention will comprise three cycles of 5 minutes of inflation followed by 5 minutes of deflation of a pneumatic tourniquet placed in mid-thigh. Pneumatic tourniquet: Portable Tourniquet System(PTSii, Delfi Medical Innovations, Inc.) used to perform RIC interventions.	Historical Control Cohort n=63 participants at risk Subjects in this cohort were chosen via retrospective record review, and selected applying the same inclusion and exclusion criteria as in the RIC cohort. They were chosen consecutively in revere-chronological order that began at the start of the study date. Target ratio of RIC:Controls was 1:2. No matching was performed for age, sex, and model for end stage liver disease (MELD) score.
Musculoskeletal and connective tissue disorders Pain due to intervention	19.4% 6/31 • Number of events 6 • Adverse events will be tracked for the first 30 days post-transplant. In addition to the clinical.trials. gov definitions, adverse events will be monitored related to the RIC intervention: Withdrawal of consent due to discomfort/pain in the lower extremity. Any other adverse event considered by the primary clinical team to be related to the RIC intervention.	0.00% 0/63 • Adverse events will be tracked for the first 30 days post-transplant. In addition to the clinical.trials. gov definitions, adverse events will be monitored related to the RIC intervention: Withdrawal of consent due to discomfort/pain in the lower extremity. Any other adverse event considered by the primary clinical team to be related to the RIC intervention.

Additional Information

Baburao Koneru, MD, MPH

Rutgers-NJ Medical School

Phone: 973-972-9599

Email: koneruba@njms.rutgers.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place