Remote Ischaemic Preconditioning in Transplantation (RIPTRANS)

Study Overview
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Brief Summary
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Remote ischemic preconditioning (RIPC) is a concept where remotely induced ischemia produces protection against ischemia-reperfusion injury in a remote organ. RIPC has been studied extensively in animal models and heart surgery, but it's benefit in transplantation has been studied less. The primary aim of this study is to find out whether RIPC performed in a donor in donation after brain-death (DBD) could improve delayed graft function rate of kidney transplants.

Official Title
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Remote Ischaemic Preconditioning in Transplantation (RIPTRANS) - A Prospective Randomized Controlled Trial

Conditions
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Transplant Dysfunction

Intervention / Treatment
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* Procedure: RIPC
* Procedure: Sham-RIPC


Participation Criteria
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Eligibility Criteria
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Donor Inclusion Criteria: Brain-dead organ donor with a plan of harvesting at least one kidney Donor Exclusion Criteria: Haemodynamically unstable donor Age below 18 years Planned organ recipients are recruited to another prospective trial, which prevents participation in this trial. All organ recipients receiving organs (kidney, liver, pancreas-kidney, heart, lungs) from a randomized donor will be recruited providing that the recipient surgery is performed at Helsinki University Hospital, recipient is over 18 years old, and recipient gives written informed consent to participate in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIPC<br>RIPC will consist of setting a tourniquet to donor thigh and inflating it to 300mmHg four times 5 minutes with 5 minutes deflating in between each. RIPC-intervention will be performed twice: First after brain death and second time before procurement procedure. | Procedure: RIPC<br>* Remote Ischaemic Preconditioning<br>|
| Sham Comparator: Sham-RIPC<br>Sham-RIPC will consist of setting a tourniquet to donor thigh without inflating it and keeping it in place for 35 min. Sham-RIPC-intervention will be performed twice: First after brain death and second time before procurement procedure. | Procedure: Sham-RIPC<br>* Sham procedure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DGF | Delayed graft function of kidney allografts defined as postoperative dialysis within 1 week from transplantation | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney allografts: eGFR | Kidney allografts: estimated glomerular filtration rate | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Combined Pancreas-Kidney allografts: eGFR | Combined Pancreas-Kidney allografts: estimated glomerular filtration rate | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Kidney allografts: BPAR | Kidney allografts: Biopsy proven acute rejection | within 1 year | 
| Combined Pancreas-Kidney allografts: Kidney BPAR | Combined Pancreas-Kidney allografts: Biopsy proven acute rejection in Kidney allograft | within 1 year | 
| Kidney allografts: graft survival | Kidney allografts: time from transplantation to death, retransplantation or permanent dialysis | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Combined Pancreas-Kidney allografts: kidney graft survival | Combined Pancreas-Kidney allografts: time from transplantation to death, retransplantation of the kidney or permanent dialysis | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Kidney allografts: death-censored graft survival | Kidney allografts: time from transplantation to retransplantation or permanent dialysis, death-censored | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Combined Pancreas-Kidney allografts: death-censored kidney graft survival | Combined Pancreas-Kidney allografts: time from transplantation to retransplantation of the kidney or permanent dialysis, death-censored | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Liver allografts: MEAF-score at 3rd POD | Liver allografts: Model for Early Allograft Function Scoring (MEAF) (MEAF = (score ALTmax:3POD+ score INRmax:3POD+ score bilirubin3POD), score range 0 - 10, higher score indicates worse outcome) | 3rd post-operative day | 
| Liver allografts: Postoperative biliary complications | Liver allografts: Amount and type of postoperative biliary complications: stricture at anastomosis, bile leak, ischaemic type biliary lesions (ITBL) | within 1 year | 
| Liver allografts: Posttransplantation kidney injury | Liver allografts: Posttransplantation kidney injury (acute kidney injury) according to ADQI (2010) criteria | within 1 week, at 3 months, 1 year | 
| Liver allografts: BPAR | Liver allografts: Biopsy proven acute rejection | within 1 year | 
| Liver allografts: graft survival | Liver allografts: graft survival: time from transplantation to death, retransplantation or explantation | at 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Pancreas allografts: HbA1c | Pancreas allografts: blood HbA1c measurement | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Pancreas allografts: Acute rejection | Pancreas allografts: Either biopsy proven (allograft pancreas or duodenal biopsy) acute rejection or clinically treated suspected acute rejection | within 1 year | 
| Pancreas allografts: Pancreatic allograft survival | Pancreas allografts: Time from transplantation to death, retransplantation, explantation or daily insulin dependance | at 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Pancreas allografts: Death-censored Pancreatic allograft survival | Pancreas allografts: Time from transplantation to retransplantation, explantation or daily insulin dependance, death-censored | at 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Heart allograft: TnI at 6 hours | Heart allograft: blood TnI measurement at 6 hours after transplantation | at 6 hours | 
| Heart allograft: proBNP at 1 week | Heart allograft: blood proBNP measurement at 1 week after transplantation (12/09/2019 BNP changed to proBNP because of changes in Helsinki University Hospital HUSlab laboratory protocols) | at 1 week | 
| Heart allograft: Primary graft dysfunction | Heart allograft: Primary graft dysfunction according to ISHLT (2014) | within 24 hours after transplantation | 
| Heart allograft: acute rejection | Heart allograft: Biopsy proven or clinically treated acute rejection | within 1 year | 
| Heart allograft: Vasculopathy-free survival | Heart allograft: Vasculopathy-free survival according to Mehra (2010) | at 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Heart allograft: graft survival | Heart allograft: time from transplantation to death, retransplantation or explantation | at 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Lung allograft: Primary graft dysfunction | Lung allograft: Primary graft dysfunction according to ISHLT | within 72 hours | 
| Lung allograft: Acute rejection | Lung allograft: Biopsy proven or clinically treated acute rejection | within 1 year | 
| Lung allograft: CLAD-free survival | Lung allograft: Chronic Lung Allograft Dysfunction (CLAD) free survival according to Verleden (2014) | at 1 year, 2 year, 5 year, 10 year, and 20 year | 
| Lung allograft: graft survival | Lung allograft: time from transplantation to death, retransplantation or explantation (12/16/2019 secondary outcome measures for lung recipients redifined. Lung recipients recruitment started later than for other organs because of a conflicting trial which now has completed recruiting. Only four lung patients have thus far been included in the study and no results for lung recipients have been analyzed.) | at 1, 2, 5, 10 and 20 year |