Trial Outcomes & Findings for Remote Ischemic Preconditioning in Neurological Death Organ Donors (NCT NCT01515072)

NCT ID: NCT01515072

Last Updated: 2018-12-19

Results Overview

Number of organs recovered per organ donor

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 321 participants
• Primary outcome timeframe: At time of organ recovery, up to 1 day
• Results posted on: 2018-12-19

Participant Flow

The RIPNOD trial was conducted from July 2011 to July 2014 in two organ procurement organizations (OPO) in the U.S. Consent for research was obtained from donors next of kin by the OPO staff unless a 'first person' consent existed.

Participant milestones

Measure	No RIPC The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Overall Study STARTED	166	155
Overall Study COMPLETED	166	155
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Data missing for 2 participants in each arm of the study.

Baseline characteristics by cohort

Measure	No RIPC n=166 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=155 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.	Total n=321 Participants Total of all reporting groups
Age, Continuous	44 years n=166 Participants	42 years n=155 Participants	43 years n=321 Participants
Age, Customized 11-25	24 participants n=166 Participants	34 participants n=155 Participants	58 participants n=321 Participants
Age, Customized 26-35	39 participants n=166 Participants	27 participants n=155 Participants	66 participants n=321 Participants
Age, Customized 36-45	26 participants n=166 Participants	34 participants n=155 Participants	60 participants n=321 Participants
Age, Customized 46-75	77 participants n=166 Participants	60 participants n=155 Participants	137 participants n=321 Participants
Sex: Female, Male Female	59 Participants n=166 Participants	62 Participants n=155 Participants	121 Participants n=321 Participants
Sex: Female, Male Male	107 Participants n=166 Participants	93 Participants n=155 Participants	200 Participants n=321 Participants
Race/Ethnicity, Customized White	97 participants n=166 Participants	74 participants n=155 Participants	171 participants n=321 Participants
Race/Ethnicity, Customized African-American	35 participants n=166 Participants	42 participants n=155 Participants	77 participants n=321 Participants
Race/Ethnicity, Customized Hispanic	30 participants n=166 Participants	38 participants n=155 Participants	68 participants n=321 Participants
Race/Ethnicity, Customized Other	4 participants n=166 Participants	1 participants n=155 Participants	5 participants n=321 Participants
Region of Enrollment United States	166 participants n=166 Participants	155 participants n=155 Participants	321 participants n=321 Participants
Body Mass Index (BMI) BMI < 30.0	126 participants n=166 Participants	104 participants n=155 Participants	230 participants n=321 Participants
Body Mass Index (BMI) BMI =/> 30.0	40 participants n=166 Participants	51 participants n=155 Participants	91 participants n=321 Participants
Hepatitis C Antibody Yes	7 participants n=166 Participants	16 participants n=155 Participants	23 participants n=321 Participants
Hepatitis C Antibody No	159 participants n=166 Participants	139 participants n=155 Participants	298 participants n=321 Participants
Co-Morbidities Hypertension: Yes	58 participants n=166 Participants	48 participants n=155 Participants	106 participants n=321 Participants
Co-Morbidities Hypertension: No	108 participants n=166 Participants	107 participants n=155 Participants	215 participants n=321 Participants
Central Line Use Yes	121 participants n=166 Participants	116 participants n=155 Participants	237 participants n=321 Participants
Central Line Use No	45 participants n=166 Participants	39 participants n=155 Participants	84 participants n=321 Participants
Co-Morbidities Diabetes: Yes	19 participants n=166 Participants	21 participants n=155 Participants	40 participants n=321 Participants
Co-Morbidities Diabetes: No	147 participants n=166 Participants	134 participants n=155 Participants	281 participants n=321 Participants
Co-Morbidities Past or Current Smoker:Yes	89 participants n=166 Participants	99 participants n=155 Participants	188 participants n=321 Participants
Co-Morbidities Past or Current Smoker:No	77 participants n=166 Participants	56 participants n=155 Participants	133 participants n=321 Participants
Steroids Administered Steroids Administered: Yes	125 participants n=166 Participants	122 participants n=155 Participants	247 participants n=321 Participants
Steroids Administered Steroids Administered: No	41 participants n=166 Participants	33 participants n=155 Participants	74 participants n=321 Participants
Insulin Infusion Insulin Infusion: Yes	47 participants n=166 Participants	42 participants n=155 Participants	89 participants n=321 Participants
Insulin Infusion Insulin Infusion: No	119 participants n=166 Participants	113 participants n=155 Participants	232 participants n=321 Participants
Declaration of Death to Initial Intervention, Hours	5.8 hours n=166 Participants	7.3 hours n=155 Participants	6.5 hours n=321 Participants
Initial Intervention to Cross Clamp Intervention to Cross Clamp: 5.9-24.0 hours	123 participants n=166 Participants	115 participants n=155 Participants	238 participants n=321 Participants
Initial Intervention to Cross Clamp Intervention to Cross Clamp: 24.1-39.5 hours	35 participants n=166 Participants	25 participants n=155 Participants	60 participants n=321 Participants
Initial Intervention to Cross Clamp Intervention to Cross Clamp: Data not available	8 participants n=166 Participants	15 participants n=155 Participants	23 participants n=321 Participants
Vasopressor Score	100 units on a scale n=164 Participants • Data missing for 2 participants in each arm of the study.	16.0 units on a scale n=153 Participants • Data missing for 2 participants in each arm of the study.	37 units on a scale n=317 Participants • Data missing for 2 participants in each arm of the study.
P:F ratio	249.8 ratio n=166 Participants	244.0 ratio n=155 Participants	248 ratio n=321 Participants
Ventricular Ejection Fraction	0.6 proportion ejection fraction n=166 Participants	0.59 proportion ejection fraction n=155 Participants	0.6 proportion ejection fraction n=321 Participants
Serum Chemistry: Creatinine	1.0 mg/dL n=166 Participants	1.1 mg/dL n=155 Participants	1.06 mg/dL n=321 Participants
Serum Chemistry: Lactate	1.5 mg/dL n=166 Participants	1.6 mg/dL n=155 Participants	1.6 mg/dL n=321 Participants
Serum Chemistry: Troponin I	0.28 ng/ml n=166 Participants	0.31 ng/ml n=155 Participants	0.29 ng/ml n=321 Participants

PRIMARY outcome

Timeframe: At time of organ recovery, up to 1 day

Population: Subjects were organ donors enrolled in this multicenter study

Number of organs recovered per organ donor

Outcome measures

Measure	No RIPC n=166 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=155 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Number of Organs Recovered Per Donor	3.79 organs recovered per donor Standard Deviation 1.73	3.60 organs recovered per donor Standard Deviation 1.84

SECONDARY outcome

Timeframe: Within 24 hours of organ recovery

Population: Subjects were organ donors enrolled in this multicenter study

Number of organs transplanted from each organ donor

Outcome measures

Measure	No RIPC n=166 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=155 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Number of Organs Transplanted Per Donor	3.41 Organs transplanted from each donor Standard Deviation 1.90	3.31 Organs transplanted from each donor Standard Deviation 1.94

SECONDARY outcome

Timeframe: Vasopressor score was determined before aortic cross clamp minus the value prior to the first intervention, an average of 19 hours

Population: Donors in whom vasopressor agent and dose were described in the OPO records before intervention and prior to aortic cross clamp.

Changes in the following: Vasopressor usage, serum Lactate, Creatinine clearance, arterial oxygen pressure:fraction of inspired oxygen (P:F) ratios, Lung Compliance, Cardiac biomarkers, ejection fraction (EF) from 2-dimensional Echocardiogram.

Here we will present data for the change in vasopressor use evaluated using a vasopressor score.

A numerical score calculated for number and dose of Vasopressors in use. The score is calculated using the following formula (from Zuppa AF et. al.CRIT CARE MED 2004 Vol. 32 p 2318-2322):

Vasopressor Score= (dopamine dose[y=ug/kg/min x 1]) + (dobutamine dose [ug/kg/min] x 1) + (epinephrine dose [ug/kg/min] x100) + (norepinephrine dose [ug/kg/min] x 100) + (phenylephrine dose [ug/kg/min] x 100).

The range for our study was 0-4900 with higher doses indicating higher vasopressor use in the donor.

Outcome measures

Measure	No RIPC n=158 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=141 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Change in Vasopressor Score	-15.60 units on a scale Interval -600.0 to 0.0	-6.00 units on a scale Interval -400.0 to 0.0

SECONDARY outcome

Timeframe: Subjects will be followed from admission to explantation, an average of 4.5 days

Population: Donors in whom at least two serum lactate levels (one before and one after the initial intervention) were available

Change in serum lactate levels (mg/dL) from before intervention to the final value

Outcome measures

Measure	No RIPC n=127 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=126 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Change in Serum Lactate	0.12 mg/dL Interval -40.0 to 0.7	0.20 mg/dL Interval -40.0 to 0.6

SECONDARY outcome

Timeframe: Subjects will be followed from admission to explantation, an average of 4.5 days

Population: Donors in whom two serum creatinine values (one before intervention and another after the initial intervention) are available.

Change in creatinine clearance (mL/min by Cockcroft-Gault method) from before intervention to terminal value

Outcome measures

Measure	No RIPC n=155 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=145 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Change in Creatinine Clearance	0 mL/min Interval -8.1 to 9.8	0 mL/min Interval -10.6 to 14.4

SECONDARY outcome

Timeframe: Subjects will be followed from admission to explantation, an average of 4.5 days

Change in ratio of arterial oxygen pressure:fraction inspired oxygen ratio from before intervention to terminal value

Outcome measures

Measure	No RIPC n=152 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=142 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Change in P:F Ratio	6.5 ratio Interval -57.3 to 86.5	0.05 ratio Interval -74.3 to 96.2

SECONDARY outcome

Timeframe: Subjects will be followed from admission to explantation, an average of 4.5 days

Change in dynamic compliance of the lung from before intervention to terminal value

Cdyn = Dynamic compliance; Vt = tidal volume; PIP = Peak inspiratory pressure (the maximum pressure during inspiration); PEEP = Positive End Expiratory Pressure:

Cdyn= Vt/PIP - PEEP

Outcome measures

Measure	No RIPC n=123 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=123 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Change in Dynamic Compliance	2.30 L/cm H20 Interval -2.0 to 7.6	1.20 L/cm H20 Interval -1.8 to 8.1

SECONDARY outcome

Timeframe: Subjects will be followed from admission to explantation, an average of 4.5 days

Population: Only donors in whom two troponin I values (one before intervention and another after the initial intervention) were available were included in this analysis

Change in serum troponin I (ng/mL) from before intervention to terminal value

Outcome measures

Measure	No RIPC n=122 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=119 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Change in Troponins	-0.04 ng/mL Interval -0.38 to 0.0	-0.09 ng/mL Interval -0.69 to -0.01

SECONDARY outcome

Timeframe: Up to 24 hours of machine perfusion

Perfusate flow (mL/min) in machine perfused kidneys.

Outcome measures

Measure	No RIPC n=49 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=32 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Pulsatile Perfusion Flow Flow at 1 hour, mL/min	98.58 mL/min Standard Deviation 32.41	89.42 mL/min Standard Deviation 38.31
Pulsatile Perfusion Flow 4 hours	105.28 mL/min Standard Deviation 23.75	104.03 mL/min Standard Deviation 40.66
Pulsatile Perfusion Flow 8 hours	117.98 mL/min Standard Deviation 28.86	94.21 mL/min Standard Deviation 32.64
Pulsatile Perfusion Flow 12 hours	115.19 mL/min Standard Deviation 20.07	106.36 mL/min Standard Deviation 32.55

SECONDARY outcome

Timeframe: 6 months post-transplant

Population: Recipients of all organs from donors enrolled in the two arms

Six month hospital-free survival was defined as the number of days recipients survived following the initial discharge after the transplant.

Outcome measures

Measure	No RIPC n=482 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=456 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Six Month Hospital Free Survival of All Organ Recipients	172 days Interval 165.0 to 174.0	171 days Interval 165.0 to 174.0

SECONDARY outcome

Timeframe: 7 days post-transplant

Population: Kidney recipients of donors in each arm.

DGF is defined as the need for dialysis within the first week post transplantation.

Outcome measures

Measure	No RIPC n=247 Kidney Recipients The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=235 Kidney Recipients The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Delayed Graft Function (DGF) of Kidney Recipients. DGF: Yes	45 participants	51 participants
Delayed Graft Function (DGF) of Kidney Recipients. DGF: No	202 participants	184 participants

SECONDARY outcome

Timeframe: Up to 24 hours of machine perfusion

Perfusate resistance (mm Hg/mL/min) in machine perfused kidneys.

Outcome measures

Measure	No RIPC n=49 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=32 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Pulsatile Perfusion Parameters Resistance at 1 hour, mL/min	0.29 Resistance, mm Hg/mL/min Standard Deviation 0.12	0.38 Resistance, mm Hg/mL/min Standard Deviation 0.30
Pulsatile Perfusion Parameters Resistance at 4 hours, mL/min	0.25 Resistance, mm Hg/mL/min Standard Deviation 0.10	0.31 Resistance, mm Hg/mL/min Standard Deviation 0.23
Pulsatile Perfusion Parameters Resistance at 8 hours, mL/min	0.22 Resistance, mm Hg/mL/min Standard Deviation 0.09	0.33 Resistance, mm Hg/mL/min Standard Deviation 0.23
Pulsatile Perfusion Parameters Resistance at 12 hours, mL/min	0.22 Resistance, mm Hg/mL/min Standard Deviation 0.08	0.29 Resistance, mm Hg/mL/min Standard Deviation 0.22

POST_HOC outcome

Timeframe: 6 months after kidney transplantation

Population: This outcome was examined in recipients of in SRTR that received kidneys from donors in the RIPNOD trial

Diagnosis of rejection as documented in the recipient records in the Scientific Registry of Transplant Recipients (SRTR).

Outcome measures

Measure	No RIPC n=247 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=235 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Acute Kidney Rejection Rejection: Yes	17 participants	13 participants
Acute Kidney Rejection Rejection: No	230 participants	222 participants

POST_HOC outcome

Timeframe: Graft survival was monitored from transplant date until retransplantation or death up to 2 years as in SRTR data file October 2015

Population: All grafts transplanted from donors in the RIPNOD trial and in whom recipient records are available in SRTR were included in this analysis. Graft loss is defined as retransplantation or death during the 24 months post-transplant.

Kaplan-Meier estimates of 6, 12 and 24 months survival of all grafts

Outcome measures

Measure	No RIPC n=523 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=489 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Graft Survival 6 months graft survival	91.3 percentage of all grafts	94.6 percentage of all grafts
Graft Survival 12 months	88.8 percentage of all grafts	92.2 percentage of all grafts
Graft Survival 24 months	82.2 percentage of all grafts	87.8 percentage of all grafts

POST_HOC outcome

Timeframe: Kidney graft survival was monitored from transplant date until retransplantation or death up to 2 years as in SRTR data file October 2015

Population: Included were kidneys transplanted alone or with pancreas. All kidney grafts transplanted from donors in the RIPNOD trial and in whom recipient records are available in SRTR were included in this analysis. Kidney graft loss is defined as loss of functioning graft or retransplantation during the 24 months post-transplant.

kidney graft survival censored for death with functioning graft

Outcome measures

Measure	No RIPC n=247 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=235 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Death-Censored Kidney Graft Survival at 6, 12 and 24 Months 12 months	92.5 percentage of participants	96.8 percentage of participants
Death-Censored Kidney Graft Survival at 6, 12 and 24 Months 24 months	87.4 percentage of participants	96 percentage of participants
Death-Censored Kidney Graft Survival at 6, 12 and 24 Months Death censored kidney survival: 6 months	94.2 percentage of participants	99.1 percentage of participants

POST_HOC outcome

Timeframe: Recipient survival was monitored from transplant date until death up to 2 years as in SRTR data file October 2015

Population: All recipients of organs from donors in the RIPNOD trial and in whom recipient records are available in SRTR were included in this analysis

Kaplan-Meier estimates of 6, 12 and 24 months survival of all recipients

Outcome measures

Measure	No RIPC n=494 Participants The donors assigned to this group will receive standard of care of management of brain death donors in each organ procurement organization.	RIPC n=458 Participants The donors assigned to this group would receive two RIPC interventions. The first one would occur immediately after brain death declaration and consent for organ donation. The second one would occur immediately before commencement of organ recovery. At each occasion RIPC would be induced by 4 cycles of mid-thigh inflation of tourniquet for 5 min followed by deflation for 5 minutes. RIPC (Remote Ischemic Preconditioning): Remote Ischemic Preconditioning (RIPC) by Inflation of Pneumatic Tourniquet. The intervention will consist of tourniquet inflation on the mid-thigh for 5 minutes, followed by a deflation period of 5 minutes for a total of 4 cycles. The intervention will take place at two time points: First, after determination of brain death and consent for organ donation and again upon incision for organ recovery. The second intervention will occur in a manner identical to the first intervention but in the opposite limb.
Recipient Survival Recipient survival: 6 months	92 percentage of participants	94.1 percentage of participants
Recipient Survival 12 months	90.0 percentage of participants	91.5 percentage of participants
Recipient Survival 24 months	84.4 percentage of participants	87.1 percentage of participants

Adverse Events

No RIPC, Kidney Recipients

Serious events: 45 serious events

Other events: 0 other events

Deaths: 0 deaths

RIPC, Kidney Recipients

Serious events: 51 serious events

Other events: 0 other events

Deaths: 0 deaths

No RIPC, All Organ Recipients

Serious events: 81 serious events

Other events: 0 other events

Deaths: 0 deaths

RIPC, All Organ Recipients

Serious events: 54 serious events

Other events: 0 other events

Deaths: 0 deaths

No RIPC, Donors

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

RIPC, Donors

Serious events: 14 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	No RIPC, Kidney Recipients n=247 participants at risk Recipients in this group received kidneys from donors who did not receive remote ischemic preconditioning (No RIPC group)	RIPC, Kidney Recipients n=235 participants at risk Recipients in this group received kidneys from donors who received two RIPC interventions	No RIPC, All Organ Recipients n=494 participants at risk Recipients in this group received organs from donors who did not receive remote ischemic preconditioning (No RIPC)	RIPC, All Organ Recipients n=458 participants at risk Recipients in this group received organs from donors who received two RIPC interventions	No RIPC, Donors n=166 participants at risk Donors in this group did not receive remote ischemic preconditioning (RIPC)	RIPC, Donors n=155 participants at risk Donors in this group received two RIPC interventions
Renal and urinary disorders DGF in kidney recipients	18.2% 45/247 • Number of events 45 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	21.7% 51/235 • Number of events 51 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.
Renal and urinary disorders Kidney rejection	6.9% 17/247 • Number of events 17 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	5.5% 13/235 • Number of events 13 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	0.00% 0/166 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	0.00% 0/155 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.
General disorders Grafts lost	10.5% 26/247 • Number of events 26 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	4.3% 10/235 • Number of events 10 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	16.4% 81/494 • Number of events 81 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	11.4% 52/458 • Number of events 52 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.
General disorders Recipient Deaths	9.3% 23/247 • Number of events 23 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	8.5% 20/235 • Number of events 20 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	14.0% 69/494 • Number of events 69 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	11.8% 54/458 • Number of events 54 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.
General disorders Number of Donors from which no Organs recovered	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	— 0/0 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	4.8% 8/166 • Number of events 8 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.	9.0% 14/155 • Number of events 14 Adverse events to be collected were not identified or defined a priori. In donors, data were collected from enrollment to organ recovery; recipient data for DGF in kidney recipients were abstracted from transplantation to last follow up to 2 years in SRTR. Lack of information in SRTR precluded analyses regarding the severity of DGF. Submitted followup data was available at 6, 12 and 24 months in 97.5%, 75.5% and 38.8% of recipients, respectively. Updated SRTR recipient data has been requested.

Other adverse events

Adverse event data not reported

Additional Information

Baburao Koneru, MD, MPH

Rutgers-New Jersey 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