Viewing Study NCT03150147



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Last Modification Date: 2024-10-26 @ 12:24 PM
Study NCT ID: NCT03150147
Status: COMPLETED
Last Update Posted: 2021-04-28
First Post: 2017-05-08

Brief Title: A Randomized Controlled Trial Comparing Non-ischemic to Ischemic Preservation in Adult Cardiac Transplantation
Sponsor: Region Skane
Organization: Region Skane

Study Overview

Official Title: A Randomized Controlled Trial Comparing Non-ischemic Hypothermic Cardioplegic Perfusion to Ischemic Cold Static Preservation of Donor Hearts in Adult Cardiac Transplantation
Status: COMPLETED
Status Verified Date: 2021-04
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: NIHP
Brief Summary: The overall aim of this proposal is to compare a new state-of-the-art ex-vivo organ preservation method with standard ischemic cold static storage of donor hearts in adult cardiac transplantation

Standard heart preservation before transplantation consists of cold ischemic storage of the heart Clinical studies has shown that the morbidity and mortality risk increases with extension of the allograft ischemic time over four hours For each additional hour the mortality risk increase with 25 the first year This time constrained is costly and results in severe logistical problems leading to loss of transplantable organs

Initially the study is prospective single-institution open-label non-randomised trial comparing the NIHP method with the conventionally SCS in adult heart transplanted patients at Skane University Hospital Lund Sweden Six patients will be transplanted using the non-ischemic hypothermic cardioplegic perfusion These will be compared with contemporary control patients transplanted with standard ischemic cold static storage The results will be analysed and reported

After the initially six patients have been completed the study will become a single center prospective open blinded endpoint randomized controlled clinical trial including 34 patients

The primary end-point is a composite of mortality primary graft dysfunction PGD need for extra corporal support or acute cellular rejection ACR within 30- days post-transplant PGD and ACR will be accessed blindedAn improved preservation of the transplanted organ will reduce the major limitations for survival in the early post-transplant period such as non-specific graft failure and acute rejection Furthermore it will make it possible to increase the donor pool
Detailed Description: SURVEY OF THE FIELD

Ischemia and reperfusion IR-elicited tissue injury contributes to morbidity and mortality4 In organ transplantation it is a major challenge The imbalance in metabolic supply and demand within the ischemic organ results in tissue hypoxia and microvascular dysfunction4 The following reperfusion enhances the activation of innate and adaptive immune responses resulting in a cell death programs45 Furthermore it has been report that miRNA expression profile for heart transplantation is associated with IR injury Standard heart preservation before transplantation consists of cold ischemic storage of the heart Clinical studies have shown that the mortality risk increases sharply with extension of the allograft ischemic time over 4 hours For each additional hour the mortality risk increase with 25 the first year Different myocardial cardioplegic preservation solutions and an ex-vivo perfusion machine have been developed That technique includes use of whole blood from deceased donor and a normothermic beating heart consuming nutrients during the preservation Despite some promising experimental results no consistent differences in outcome have been found Improved preservation of the endothelium of the coronary arteries is instrumental to achieve improved patient short and long term outcome A damaged endothelium could result in cardiac allograft vasculopathy CAV and increases the risk of ACR Therefore prolonged time and improved storage of the donor heart would save lives

PURPOSE AND AIM

The overall aim of this study is to compare a new state-of-the-art organ preservation technique non-ischemic continousintermittent hypothermic cardioplegic perfusion NICHCP on immediate and long term heart allograft function and rejection episodes with standard ischemic cold static storage ICSS of donor hearts in adult cardiac transplantation

A new ex-vivo heart perfusion technique where the heart is perfused during explantation using an independent portable heart-lung-machine has been developed by Prof Steens research group3 Pre-clinical studies have shown that the new technology using NICHCP of donor hearts can be safely applied for 24 hours in pigs however this new perfusion technique has never been used on man

The primary hypothesis is that the NICHCP is superior to ischemic cold static storage of donor hearts The primary end-point is a composite of mortality primary graft dysfunction need for extra corporal mechanical support or Acute Cellular Rejection ACR grade 2 within 30-days

RESEARCH QUESTION

The study will investigate the superiority of the new methodology NICHCP in terms of improved immediate and prolonged organ function More specifically it is hypothesized that the weaning period of cardio-pulmonary bypass will be shorter the need for inotropic support reduced and the major limitations for survival in the early post-transplant period such as non-specific graft failure multiorgan failure ACR and infection will decrease Furthermore in the late post-transplant period it is hypothesized that the development of CAV and immunosuppressive side effects such as malignancy will be reduced

WORK PLAN

In the initial phase it is excepted that 1 - 2 patients will be enrolled per month During the randomized part of the study It is expected to enroll 1 - 4 patients per month With that pace the study is completed within about 24 months The patient short term follow-up is 30 days and long term follow up is 12 months For short-term-analysis purpose the study is considered completed as the last patient of the study has passed 30-days post-surgery The long-term study will continue to monitor the patients for 12 months Adverse events will be recorded even if occurring after completion of the study and all patients will be followed throughout life according to standard clinical care

If this is successful this will be introduced as standard among other national and international collaborators The investigators estimate that this technique will be the golden standard within 5 years

STUDY DESIGN

Initially the study is a prospective single-institution open-label non-randomised trial Here six patients will be transplanted with the NICHCP method These will be compared with contemporary control patients transplanted with standard ICSS An interim assessment will be performed when these six patients has passed 180-days post-transplant The results from this study will be analysed and published A report will be sent to the Ethical review bord for an approval to continue with the second part of the study

After six patients have been transplanted with the NICHCP method and a new approval has been achieved from the local ethical board the study will become a single center prospective open blinded endpoint randomized controlled clinical trial The continued study will comprise 17 patients in the test group and 17 control patients The main outcomes will be reported on intention to treat basis PGD and ACR assessment will be performed by a blinded access Listed heart recipients aged 18 years at Skåne University Hospital will be screened Patients who full-fill all inclusion and no exclusion criteria will be included after they signed the informed consent form In the initial phase it is excepted that 1-2 patients will be enrolled per month During the randomized part of the study it is expected to enroll 1-4 patients per month With that pace the study is completed within 24 months The patient short term follow-up is 30 days and long term follow up is 12 months For short-term-analysis purpose the study is considered completed as the last patient of the study has passed 30-days post-surgery The long-term study will continue to monitor the patients for 12 months Adverse events will be recorded even if occurring after completion of the study and all patients will be followed throughout life according to standard clinical care

STATISTICAL ANALYS PLAN

Descriptive statistics will be presented as means standard deviations medians and inter quartile ranges for the continuous variables and as counts and percent for categorical variables An alpha level of 5 will be used for all analyses unless otherwise stated Demographics will be tabulated overall and by treatment group The results from the laboratory analysis will be calculated based on continuous variables All data analyses will be performed on data available After three of the patients have been enrolled a safety assessment will be performed An interim assessment of the initial six patients in the test group will be performed when all six patients has passed 30-days post-transplant or expired A protocol deviation is any event where investigator or study personnel did not conduct the study per the protocol or applicable laws All deviations will be reported to the Principal Investigator regardless of cause or prior approval and will be noted on the eCRF form

CLINICAL AND SCIENTIFIC IMPLICATIONS

The use of an ex-vivo machine for the preservation of a donor heart requires more resources than the technology used today such as special equipment suitable transportation and bank blood to prime the perfusion module Compared with cold static techniques for preservation this will initially be costly However this must be weighed against the value of more donor hearts become available for transplant and cost savings in the form of shorter time to perform the surgery reduced incidence of the primary graft dysfunction PGD less need for expensive mechanical cardiac support post-transplant shortened hospitalization and longer-term risk reduction of chronic rejection The costs of complications directly connected to the transplant is cost driven especially if the recipient develops PGD requiring mechanical circulatory support with a prolonged ICU stay Furthermore in the future the transplantation can be scheduled to day-time surgery and complexed high risk cases can be done with the highest competence available without time limitation An improved preservation of the transplanted organ will reduce the major limitations for survival in the early post-transplant period such as PGD Furthermore it will make it possible to increase the donor pool Theoretically in the nordic countries this would enable international organ sharing with Europe and the eastern United States This expansion of the donor pool is one of the main potential benefits of this device

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None