Clinical trial NCT02876250: Postconditioning by Cyclosporin A in Pulmonary Transplantation
Official title: Postconditioning by Cyclosporin A in Pulmonary Transplantation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Lung Transplantation
Keywords: Lung transplantation
Cyclosporine
Postconditioning
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2016-08-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The morbidity and mortality of patients undergoing lung transplantation in the acute phase following surgical intervention is mainly due to the primary graft failure (PGF).

The occurrence of PGF is multi factorial but is mainly caused by ischemia-reperfusion injury. The pulmonary graft suffers two periods of ischemia one when it is explanted from the donor (cold ischemia) followed by another when it is grafted into the recipient's thoracic cavity (warm ischemia). The brutal reperfusion of the graft exposes it to reperfusion injury that causes PGF. PGF occurs in up to 20% of transplanted patients and is associated with significantly higher levels of 30-days all-cause mortality. Patients with PGF have a 40% mortality at 30-days versus a 6% mortality in patients without PGF.

Ischemic postconditioning, has recently been described in experimental models of ischemia-reperfusion injury in the heart, and although not yet fully understood. Several studies suggest that the mitochondria play a central role in cellular survival mechanisms after a prolonged period of ischemia-reperfusion (with the mitochondrial permeability transition pore (mPTP)).

Experimental studies have shown that cyclosporin A (CsA) administered prior to reperfusion binds to cyclophilin D and blocks the opening of mPTP after reperfusion. This protective effect of ischemia-reperfusion injury by CsA has been shown in experimental studies and in clinical phase II trials in reperfused myocardial infarction patients.

The hypothesis of this study is that the administration of CsA in transplanted patients (before re-opening of the first pulmonary graft vessels) protects the transplanted lung(s) from the deleterious effects of ischemia-reperfusion injury and thus reduce the frequency and severity of PGF.


Eligibility criteria: Inclusion Criteria:

* All patients over 18 years old, man or woman, who are listed for pulmonary transplantation either mono or double lung transplantation.

Exclusion Criteria:

* No contra-indication to CsA administration.

Primary outcomes:
measure: PaO2/FiO2 ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen)
timeFrame: 2 hours post-lung transplantation
measure: PaO2/FiO2 ratio
timeFrame: 6 hours post-lung transplantation
measure: PaO2/FiO2 ratio
timeFrame: 12 hours post-lung transplantation
measure: PaO2/FiO2 ratio
timeFrame: 18 hours post-lung transplantation
measure: PaO2/FiO2 ratio
timeFrame: 24 hours post-lung transplantation
measure: PaO2/FiO2 ratio
timeFrame: 36 hours post-lung transplantation
measure: PaO2/FiO2 ratio
timeFrame: 48 hours post-lung transplantation
measure: PaO2/FiO2 ratio
timeFrame: 60 hours post-lung transplantation
measure: PaO2/FiO2 ratio
timeFrame: 72 hours post-lung transplantation
Secondary outcomes:
measure: primary graft failure grade
timeFrame: 72 hours
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Louis Pradel
Study officials:
affiliation: Hospices Civils de Lyon
name: François TRONC, Pr
role: PRINCIPAL_INVESTIGATOR
References: