Remote Ischemic Preconditioning Living Donor Renal Transplant Protocol

NCT03084666 | Terminated Results DMC FDA Device

• 1 other identifier: F130312023
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, patients undergoing live donor kidney transplantation will be allocated to the control group or remote ischemic preconditioning group (RIPC). RIPC is the utilization of short periods of ischemia to provide protection of the myocardium or other organ (i.e. kidney) from a subsequent ischemic event. Before allograft implantation, RIPC will be accomplished in the treatment group donor and control group donor by inducing intermittent extremity ischemia through intermittent inflation of an extremity tourniquet three times for five-minute intervals with five minutes of deflation between inflation periods. The monitored clinical end points will include total urine output following kidney reperfusion over five days, plasma creatinine declination over five days, initiation of dialysis, and development of graft injury. Magnitude of graft injury is the primary endpoint and will be measured using biochemical markers, such as, plasma and urinary concentration of neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1). The sample size calculation is based on a projected difference of NGAL levels between the two study arms. Hall et al reported a mean NGAL level of 49 mg/mL (SD = 37 mg/mL) for a group of patients that had immediate graph function and a mean NGAL level of 248 mg/mL in a group of patients with slow graft function. (which Hall reference is this) Based on these data, a conservative estimate of a mean difference between study groups will be considered 35 mg/mL NGAL. Using these assumptions, an alpha level of 0.05 and 80% power, a sample size of n= 19 per study group will be calculated. By rejecting our null hypothesis, RIPC may serve as a safe, cost-effective protective strategy to prevent allograft injury in the clinical setting of live donor kidney transplantation.

Conditions

Renal Disease

Outcome Measures

Primary Outcomes (5)

• Biomarkers Measured to Indicate the Magnitude of Graft Injury

  Remote ischemic preconditioning (RIPC) will be accomplished in the treatment group donor and control group donor by inducing intermittent extremity ischemia through intermittent inflation of an extremity tourniquet three times for five-minute intervals with five minutes of deflation between inflation periods. The monitored clinical end points will include total urine output following kidney reperfusion. Magnitude of graft injury is the primary endpoint and will be measured using biochemical markers, such as, plasma and urinary concentration of neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1). The sample size calculation is based on a projected difference of NGAL levels between the two study arms.

  Baseline

• Biomarkers Measured to Indicate the Magnitude of Graft Injury

  RIPC will be accomplished in the treatment group donor and control group donor by inducing intermittent extremity ischemia through intermittent inflation of an extremity tourniquet three times for five-minute intervals with five minutes of deflation between inflation periods. The monitored clinical end points will include total urine output following kidney reperfusion. Magnitude of graft injury is the primary endpoint and will be measured using biochemical markers, such as, plasma and urinary concentration of neutrophil gelatinase associated lipocalin (NGAL), IL-18, and KIM-1. The sample size calculation is based on a projected difference of NGAL levels between the two study arms.

  6 hours post-operatively

• Biomarkers Measured to Indicate the Magnitude of Graft Injury

  RIPC will be accomplished in the treatment group donor and control group donor by inducing intermittent extremity ischemia through intermittent inflation of an extremity tourniquet three times for five-minute intervals with five minutes of deflation between inflation periods. The monitored clinical end points will include total urine output following kidney reperfusion. Magnitude of graft injury is the primary endpoint and will be measured using biochemical markers, such as, plasma and urinary concentration of neutrophil gelatinase associated lipocalin (NGAL), IL-18, and KIM-1. The sample size calculation is based on a projected difference of NGAL levels between the two study arms.

  12 hours post-operatively

• Biomarkers Measured to Indicate the Magnitude of Graft Injury

  RIPC will be accomplished in the treatment group donor and control group donor by inducing intermittent extremity ischemia through intermittent inflation of an extremity tourniquet three times for five-minute intervals with five minutes of deflation between inflation periods. The monitored clinical end points will include total urine output following kidney reperfusion. Magnitude of graft injury is the primary endpoint and will be measured using biochemical markers, such as, plasma and urinary concentration of neutrophil gelatinase associated lipocalin (NGAL), IL-18, and KIM-1. The sample size calculation is based on a projected difference of NGAL levels between the two study arms.

  24 hours post-operatively

• Biomarkers Measured to Indicate the Magnitude of Graft Injury

  RIPC will be accomplished in the treatment group donor and control group donor by inducing intermittent extremity ischemia through intermittent inflation of an extremity tourniquet three times for five-minute intervals with five minutes of deflation between inflation periods. The monitored clinical end points will include total urine output following kidney reperfusion. Magnitude of graft injury is the primary endpoint and will be measured using biochemical markers, such as, plasma and urinary concentration of neutrophil gelatinase associated lipocalin (NGAL), IL-18, and KIM-1. The sample size calculation is based on a projected difference of NGAL levels between the two study arms.

  48 hours post-operatively

Secondary Outcomes (3)

• Number of Participants That Experienced a Mortality Event

  From baseline through 90 days

• Length of ICU Stay

  from baseline through 90 days

• Overall Length of Hospital Stay

  from baseline through 90 days

Study Arms (2)

Treatment Group

EXPERIMENTAL

The treatment will receive 200 mmHg of pressure from a Zimmer automatic tourniquet system (ATS) for three 5 minute intervals.

Device: Zimmer ATS tourniquet system

Control Group

EXPERIMENTAL

Our control group will receive 20 mmHg of pressure from a Zimmer automatic tourniquet system (ATS) for three 5 minute intervals.

Device: Zimmer ATS tourniquet system

Interventions

Zimmer ATS tourniquet system DEVICE

The tourniquet is the same kind that is used in orthopedic surgeries to limit blood loss in arm or leg surgery. It can be inflated to a set pressure for a set amount of time.

Control Group; Treatment Group

Eligibility Criteria

• Age: 19 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> OR = 19 years of age receiving a living donor renal transplant (treatment control group) and their donors (control group donors)

You may not qualify if:

• \< 19 years of age
• No safe extremity to place tourniquet
• Patients with previous muscle, vascular, or nerve injury to an extremity,
• Patients with only one available extremity that has an arteriovenous fistula
• Patients who are hemodialysis dependent who have not received hemodialysis in the past 4 days
• Paraplegic/quadriplegic patients
• Active pathologic cutaneous lesions on extremities
• Patients with a history of tourniquet pain or complex regional pain syndrome (CRPS)
• Pregnant patients

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

UAB Department of Anesthesiology and Perioperative Medicine

Birmingham, Alabama, 35249, United States

Location

MeSH Terms

Conditions

Kidney Diseases

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Brant Wagener, MD, PhD
• Organization: University of Alabama at Birmingham

bwagener@uabmc.edu

12059346007

Study Officials

• Mali Mathru, MD

  UAB Department of Anesthesiology and Perioperative Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: In this study, patients undergoing live donor kidney transplantation will be allocated to the control group or remote ischemic preconditioning group (RIPC). RIPC is the utilization of short periods of ischemia to provide protection of the myocardium or other organ (i.e. kidney) from a subsequent ischemic event.

Study Record Dates

• First Submitted: March 14, 2017
• First Posted: March 21, 2017
• Study Start: July 2, 2014
• Primary Completion: May 20, 2021
• Study Completion: May 20, 2021
• Last Updated: May 12, 2022
• Results First Posted: May 12, 2022

Record last verified: 2022-04

Locations

US (1)