Transplant Dysfunction
Conditions
Brief 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.
Interventions
PROCEDURERIPC
Remote Ischaemic Preconditioning
PROCEDURESham-RIPC
Sham procedure
Sponsors
Finska Läkaresällskapet (funding)
Academy of Finland
Helsinki University Hospital Research Funds (funding)
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DGF | 7 days | Delayed graft function of kidney allografts defined as postoperative dialysis within 1 week from transplantation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combined Pancreas-Kidney allografts: eGFR | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | Combined Pancreas-Kidney allografts: estimated glomerular filtration rate |
| Kidney allografts: BPAR | within 1 year | Kidney allografts: Biopsy proven acute rejection |
| Combined Pancreas-Kidney allografts: Kidney BPAR | within 1 year | Combined Pancreas-Kidney allografts: Biopsy proven acute rejection in Kidney allograft |
| Kidney allografts: graft survival | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | Kidney allografts: time from transplantation to death, retransplantation or permanent dialysis |
| Combined Pancreas-Kidney allografts: kidney graft survival | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | Combined Pancreas-Kidney allografts: time from transplantation to death, retransplantation of the kidney or permanent dialysis |
| Kidney allografts: death-censored graft survival | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | Kidney allografts: time from transplantation to retransplantation or permanent dialysis, death-censored |
| Combined Pancreas-Kidney allografts: death-censored kidney graft survival | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | Combined Pancreas-Kidney allografts: time from transplantation to retransplantation of the kidney or permanent dialysis, death-censored |
| Liver allografts: MEAF-score at 3rd POD | 3rd post-operative day | 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) |
| Liver allografts: Postoperative biliary complications | within 1 year | Liver allografts: Amount and type of postoperative biliary complications: stricture at anastomosis, bile leak, ischaemic type biliary lesions (ITBL) |
| Liver allografts: Posttransplantation kidney injury | within 1 week, at 3 months, 1 year | Liver allografts: Posttransplantation kidney injury (acute kidney injury) according to ADQI (2010) criteria |
| Liver allografts: BPAR | within 1 year | Liver allografts: Biopsy proven acute rejection |
| Liver allografts: graft survival | at 1 year, 2 year, 5 year, 10 year, and 20 year | Liver allografts: graft survival: time from transplantation to death, retransplantation or explantation |
| Pancreas allografts: HbA1c | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | Pancreas allografts: blood HbA1c measurement |
| Kidney allografts: eGFR | at 3 months, 1 year, 2 year, 5 year, 10 year, and 20 year | Kidney allografts: estimated glomerular filtration rate |
| Pancreas allografts: Pancreatic allograft survival | at 1 year, 2 year, 5 year, 10 year, and 20 year | Pancreas allografts: Time from transplantation to death, retransplantation, explantation or daily insulin dependance |
| Pancreas allografts: Death-censored Pancreatic allograft survival | at 1 year, 2 year, 5 year, 10 year, and 20 year | Pancreas allografts: Time from transplantation to retransplantation, explantation or daily insulin dependance, death-censored |
| Heart allograft: TnI at 6 hours | at 6 hours | Heart allograft: blood TnI measurement at 6 hours after transplantation |
| Heart allograft: proBNP at 1 week | 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) |
| Heart allograft: Primary graft dysfunction | within 24 hours after transplantation | Heart allograft: Primary graft dysfunction according to ISHLT (2014) |
| Heart allograft: acute rejection | within 1 year | Heart allograft: Biopsy proven or clinically treated acute rejection |
| Heart allograft: Vasculopathy-free survival | at 1 year, 2 year, 5 year, 10 year, and 20 year | Heart allograft: Vasculopathy-free survival according to Mehra (2010) |
| Heart allograft: graft survival | at 1 year, 2 year, 5 year, 10 year, and 20 year | Heart allograft: time from transplantation to death, retransplantation or explantation |
| Lung allograft: Primary graft dysfunction | within 72 hours | Lung allograft: Primary graft dysfunction according to ISHLT |
| Lung allograft: Acute rejection | within 1 year | Lung allograft: Biopsy proven or clinically treated acute rejection |
| Lung allograft: CLAD-free survival | at 1 year, 2 year, 5 year, 10 year, and 20 year | Lung allograft: Chronic Lung Allograft Dysfunction (CLAD) free survival according to Verleden (2014) |
| Lung allograft: graft survival | at 1, 2, 5, 10 and 20 year | 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.) |
| Pancreas allografts: Acute rejection | within 1 year | Pancreas allografts: Either biopsy proven (allograft pancreas or duodenal biopsy) acute rejection or clinically treated suspected acute rejection |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: leuc | at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours | Severity of ischemia/reperfusion injury after transplantation blood leukocyte count |
| Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: neut | at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours | Severity of ischemia/reperfusion injury after transplantation neutrophil count |
| Exploratory outcomes lung allografts: FEV1 | at 1 month, 3 months, 6 months, 12 months | Exploratory outcomes lung allografts: FEV1 |
| Exploratory outcomes Kidney allograft miR-21 | peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion | Measurement of reperfusion injury in blood and urine samples micro-RNA miR-21 |
| Exploratory outcomes lung allografts: chronic rejection | at 1 month, 3 months, 6 months, 12 months | Exploratory outcomes lung allografts: chronic rejection |
| Exploratory outcomes lung allografts: infections | at 1 month, 3 months, 6 months, 12 months | Exploratory outcomes lung allografts: infections after transplantation |
| Exploratory outcomes lung allografts: FVC | at 1 month, 3 months, 6 months, 12 months | Exploratory outcomes lung allografts: FVC |
| Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: non-standardized P/F-ratio | at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours | Severity of ischemia/reperfusion injury after transplantation: non-standardized P/F-ratio during mechanical ventilation |
| Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: lactate | at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours | Severity of ischemia/reperfusion injury after transplantation , plasma lactate, |
| Exploratory outcomes Kidney allograft miR-24 | peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion | Measurement of reperfusion injury in blood and urine samples micro-RNA miR-24 |
| Exploratory outcomes Kidney allograft NGAL | peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion | Measurement of reperfusion injury in blood and urine samples neutrophil gelatinase associated lipocain NGAL |
| Exploratory outcomes Kidney allograft KIM-1 | peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion | Measurement of reperfusion injury in blood and urine samples kidney injury molecule -1 KIM-1 |
| Exploratory outcomes Kidney allograft FABP-1 | peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion | Measurement of reperfusion injury in blood and urine samples fatty acid binding protein -1 FABP-1 |
| Exploratory outcomes Kidney allograft SLPI | peroperative blood samples before and after graft perfusion and urinary sample 6 hours after transplantion | Measurement of reperfusion injury in blood and urine samples secretory leucocyte proteinase inhibitor SLPI |
| Exploratory outcomes Liver allograft: Early allograft dysfunction | at 7 days | Exploratory outcomes Liver allograft: Early allograft dysfunction according to Olthoff (Bil \>100, INR 1.6 or more, ALT or AST \> 2000 at 7th POD |
| Exploratory outcomes Liver allograft: Highest ALT within 7th POD | within 7 days | Exploratory outcomes Liver allograft: The highest ALT measurement within 7th POD |
| Exploratory outcomes Liver allograft: Highest INR within 7th POD | within 7 days | Exploratory outcomes Liver allograft: The highest INR measurement within 7th POD |
| Exploratory outcomes Liver allograft: Highest Bil within 7th POD | within 7 days | Exploratory outcomes Liver allograft: The highest Bil measurement within 7th POD |
| Exploratory outcomes heart allografts: TnI | at 1 hour, 12 hours and 24 hours | Exploratory outcomes heart allografts: TnI measurement |
| Exploratory outcomes heart allografts: proBNP | at 1 day, 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: (12/09/2019 BNP changed to proBNP because of changes in Helsinki University Hospital HUSlab laboratory protocols) |
| Exploratory outcomes heart allografts: crea | at 1 day, 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: crea |
| Exploratory outcomes heart allografts: urea | at 1 day, 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: urea |
| Exploratory outcomes heart allografts: eGFR | at 1 day, 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: eGFR |
| Exploratory outcomes heart allografts: LVEF | at 1 day, 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: left ventricle ejection fraction |
| Exploratory outcomes heart allografts: LV wall thickness | at 1 day, 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: left ventricle wall thickness measurements |
| Exploratory outcomes heart allografts: tricuspidal leak | at 1 day, 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: grading of the tricuspidal valve leak |
| Exploratory outcomes heart allografts: Ischaemia-reperfusion injury | at 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: The appearance of ischaemia-reperfusion injury in routine biopsies |
| Exploratory outcomes heart allografts: fibrosis | at 7 days, 14 days and 21 days | Exploratory outcomes heart allografts: The appearance of fibrosis associated factors in routine biopsies |
| Exploratory outcomes heart allografts: long time follow-up of proBNP | at 1 month, 3 months, 6 months, 12 months | 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) |
| Exploratory outcomes heart allografts: long time follow-up of LVEF | at 1 month, 3 months, 6 months, 12 months | Exploratory outcomes heart allografts: long time follow-up of left ventricle ejection fraction in cardiac ECHO |
| Exploratory outcomes heart allografts: CAD at 1 year | at 1 year | Exploratory outcomes heart allografts: Coronary Artery Disease in coronary angiography at 1 year |
| Exploratory outcomes heart allografts: MACE | at 1 month, 3 months, 6 months, 12 months | 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) |
| Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury standardized P/F-ratio | at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours | Severity of ischemia/reperfusion injury after transplantation: standardized P/F-ratio during mechanical ventilation |
| Exploratory outcomes lung allografts: Severity of ischaemia/reperfusion injury: CRP | at 0 hours, 1 hour, 6 hours, 12 hours and 24 hours | Severity of ischemia/reperfusion injury after transplantation: serum highly sensitive C-reactive protein |
Countries
Finland
Contacts
Primary ContactVille Sallinen, MD, PhD
Backup ContactAki Uutela, MD
Outcome results
None listed