Remote Ischaemic Preconditioning in Transplantation (RIPTRANS)

Transplant Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03855722
• Other study ID #: RIPTRANS
• Status: Recruiting
• Phase: N/A
• Start date: March 12, 2019
• Est. completion date: February 2042

Study information

• Verified date: March 2020
• Source: Helsinki University Central Hospital
• Contact: Ville Sallinen, MD, PhD
• Phone: +358-9-4711
• Email: ville.sallinen[@]helsinki.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 496
• Est. completion date: February 2042
• Est. primary completion date: March 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Transplant Dysfunction

Intervention

Procedure:
• RIPC
Remote Ischaemic Preconditioning
• Sham-RIPC
Sham procedure

Locations

Country	Name	City	State
Finland	Helsinki University Hospital	Helsinki

Sponsors (4)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	Academy of Finland (funding), Finska Läkaresällskapet (funding), Helsinki University Hospital Research Funds (funding)

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory outcomes Kidney allograft miR-21	Measurement of reperfusion injury in blood and urine samples micro-RNA miR-21	peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion
Other	Exploratory outcomes Kidney allograft miR-24	Measurement of reperfusion injury in blood and urine samples micro-RNA miR-24	peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion
Other	Exploratory outcomes Kidney allograft NGAL	Measurement of reperfusion injury in blood and urine samples neutrophil gelatinase associated lipocain NGAL	peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion
Other	Exploratory outcomes Kidney allograft KIM-1	Measurement of reperfusion injury in blood and urine samples kidney injury molecule -1 KIM-1	peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion
Other	Exploratory outcomes Kidney allograft FABP-1	Measurement of reperfusion injury in blood and urine samples fatty acid binding protein -1 FABP-1	peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion
Other	Exploratory outcomes Kidney allograft SLPI	Measurement of reperfusion injury in blood and urine samples secretory leucocyte proteinase inhibitor SLPI	peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion
Other	Exploratory outcomes Liver allograft: Early allograft dysfunction	Exploratory outcomes Liver allograft: Early allograft dysfunction according to Olthoff (Bil >100, INR 1.6 or more, ALT or AST > 2000 at 7th POD	at 7 days
Other	Exploratory outcomes Liver allograft: Highest ALT within 7th POD	Exploratory outcomes Liver allograft: The highest ALT measurement within 7th POD	within 7 days
Other	Exploratory outcomes Liver allograft: Highest INR within 7th POD	Exploratory outcomes Liver allograft: The highest INR measurement within 7th POD	within 7 days
Other	Exploratory outcomes Liver allograft: Highest Bil within 7th POD	Exploratory outcomes Liver allograft: The highest Bil measurement within 7th POD	within 7 days
Other	Exploratory outcomes heart allografts: TnI	Exploratory outcomes heart allografts: TnI measurement	at 1 hour, 12 hours and 24 hours
Other	Exploratory outcomes heart allografts: proBNP	Exploratory outcomes heart allografts: (12/09/2019 BNP changed to proBNP because of changes in Helsinki University Hospital HUSlab laboratory protocols)	at 1 day, 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: crea	Exploratory outcomes heart allografts: crea	at 1 day, 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: urea	Exploratory outcomes heart allografts: urea	at 1 day, 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: eGFR	Exploratory outcomes heart allografts: eGFR	at 1 day, 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: LVEF	Exploratory outcomes heart allografts: left ventricle ejection fraction	at 1 day, 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: LV wall thickness	Exploratory outcomes heart allografts: left ventricle wall thickness measurements	at 1 day, 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: tricuspidal leak	Exploratory outcomes heart allografts: grading of the tricuspidal valve leak	at 1 day, 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: Ischaemia-reperfusion injury	Exploratory outcomes heart allografts: The appearance of ischaemia-reperfusion injury in routine biopsies	at 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: fibrosis	Exploratory outcomes heart allografts: The appearance of fibrosis associated factors in routine biopsies	at 7 days, 14 days and 21 days
Other	Exploratory outcomes heart allografts: long time follow-up of proBNP	Exploratory outcomes heart allografts: long time follow-up of proBNP (12/09/2019 BNP changed to proBNP because of changes in Helsinki University Hospital HUSlab laboratory protocols)	at 1 month, 3 months, 6 months, 12 months
Other	Exploratory outcomes heart allografts: long time follow-up of LVEF	Exploratory outcomes heart allografts: long time follow-up of left ventricle ejection fraction in cardiac ECHO	at 1 month, 3 months, 6 months, 12 months
Other	Exploratory outcomes heart allografts: CAD at 1 year	Exploratory outcomes heart allografts: Coronary Artery Disease in coronary angiography at 1 year	at 1 year
Other	Exploratory outcomes heart allografts: MACE	Exploratory outcomes heart allografts: Major Adverse Cardiac Events (including death because of cardiac cause, graft loss, primary allograft dysfunction, rejection classified as 2R or more)	at 1 month, 3 months, 6 months, 12 months
Other	Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury standardized P/F-ratio	Severity of ischemia/reperfusion injury after transplantation: standardized P/F-ratio during mechanical ventilation	at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours
Other	Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: non-standardized P/F-ratio	Severity of ischemia/reperfusion injury after transplantation: non-standardized P/F-ratio during mechanical ventilation	at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours
Other	Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: lactate	Severity of ischemia/reperfusion injury after transplantation , plasma lactate,	at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours
Other	Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: CRP	Severity of ischemia/reperfusion injury after transplantation: serum highly sensitive C-reactive protein	at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours
Other	Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: leuc	Severity of ischemia/reperfusion injury after transplantation blood leukocyte count	at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours
Other	Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: neut	Severity of ischemia/reperfusion injury after transplantation neutrophil count	at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours
Other	Exploratory outcomes lung allografts: FEV1	Exploratory outcomes lung allografts: FEV1	at 1 month, 3 months, 6 months, 12 months
Other	Exploratory outcomes lung allografts: FVC	Exploratory outcomes lung allografts: FVC	at 1 month, 3 months, 6 months, 12 months
Other	Exploratory outcomes lung allografts: chronic rejection	Exploratory outcomes lung allografts: chronic rejection	at 1 month, 3 months, 6 months, 12 months
Other	Exploratory outcomes lung allografts: infections	Exploratory outcomes lung allografts: infections after transplantation	at 1 month, 3 months, 6 months, 12 months
Primary	DGF	Delayed graft function of kidney allografts defined as postoperative dialysis within 1 week from transplantation	7 days
Secondary	Kidney allografts: eGFR	Kidney allografts: estimated glomerular filtration rate	at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year
Secondary	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
Secondary	Kidney allografts: BPAR	Kidney allografts: Biopsy proven acute rejection	within 1 year
Secondary	Combined Pancreas-Kidney allografts: Kidney BPAR	Combined Pancreas-Kidney allografts: Biopsy proven acute rejection in Kidney allograft	within 1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Liver allografts: BPAR	Liver allografts: Biopsy proven acute rejection	within 1 year
Secondary	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
Secondary	Pancreas allografts: HbA1c	Pancreas allografts: blood HbA1c measurement	at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year
Secondary	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
Secondary	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
Secondary	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
Secondary	Heart allograft: TnI at 6 hours	Heart allograft: blood TnI measurement at 6 hours after transplantation	at 6 hours
Secondary	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
Secondary	Heart allograft: Primary graft dysfunction	Heart allograft: Primary graft dysfunction according to ISHLT (2014)	within 24 hours after transplantation
Secondary	Heart allograft: acute rejection	Heart allograft: Biopsy proven or clinically treated acute rejection	within 1 year
Secondary	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
Secondary	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
Secondary	Lung allograft: Primary graft dysfunction	Lung allograft: Primary graft dysfunction according to ISHLT	within 72 hours
Secondary	Lung allograft: Acute rejection	Lung allograft: Biopsy proven or clinically treated acute rejection	within 1 year
Secondary	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
Secondary	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