Postconditioning by Cyclosporin A in Pulmonary Transplantation

Phase 3

Withdrawn

• Conditions: Lung Transplantation
• Interventions: Drug: Cyclosporine A; Drug: Placebo

• Registration Number: NCT02876250
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-08-18
• Study First Submitted QC: 2016-08-18
• Study First Posted: 2016-08-23
• Study Start: 2017-01
• Primary Completion: 2018-09
• Study Completion: 2018-09
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-13
• Last Update Posted: 2019-03-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

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

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Exclusion Criteria

• No contra-indication to CsA administration.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyclosporine A	Cyclosporine A	a pharmacological postconditioned group with IV administration of 2.5 mg/kg of CsA prior to first graft reperfusion
Control	Placebo	a control group with IV administration of 2.5 mg/kg of placebo prior to first graft reperfusion

Primary Outcome Measures

Name	Time	Method
PaO2/FiO2 ratio	72 hours post-lung transplantation
PaO2/FiO2 ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen)	2 hours post-lung transplantation

Secondary Outcome Measures

Name	Time	Method
primary graft failure grade	72 hours	clinical status of primary graft failure at 72 hours

Trial Locations

Locations (1)

Hôpital Louis Pradel; 🇫🇷 Bron, France