Postconditioning by Cyclosporin A in Pulmonary Transplantation

NCT ID: NCT02876250

Last Updated: 2019-03-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2018-09-30

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.

Conditions

Lung Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cyclosporine A

a pharmacological postconditioned group with IV administration of 2.5 mg/kg of CsA prior to first graft reperfusion

Group Type: EXPERIMENTAL

Cyclosporine A

Intervention Type: DRUG

a pharmacological postconditioned group with IV administration of 2.5 mg/kg of CsA prior to first graft reperfusion

Control

a control group with IV administration of 2.5 mg/kg of placebo prior to first graft reperfusion

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

a control group with IV administration of 2.5 mg/kg of placebo prior to first graft reperfusion

Interventions

Cyclosporine A

a pharmacological postconditioned group with IV administration of 2.5 mg/kg of CsA prior to first graft reperfusion

Intervention Type: DRUG

Placebo

a control group with IV administration of 2.5 mg/kg of placebo prior to first graft reperfusion

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

François TRONC, Pr

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Hôpital Louis Pradel

Bron, , France

Countries

France

Other Identifiers

2013-816

Identifier Type: -

Identifier Source: org_study_id