Postconditioning by Cyclosporin A in Pulmonary Transplantation (CsA Poumon)

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.

Study Overview

• Status: Withdrawn
• Conditions: Lung Transplantation
• Intervention / Treatment: Drug: Cyclosporine A; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bron, France
    • Hôpital Louis Pradel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclosporine A; a pharmacological postconditioned group with IV administration of 2.5 mg/kg of CsA prior to first graft reperfusion	Drug: Cyclosporine A; a pharmacological postconditioned group with IV administration of 2.5 mg/kg of CsA prior to first graft reperfusion
Placebo Comparator: Control; a control group with IV administration of 2.5 mg/kg of placebo prior to first graft reperfusion	Drug: Placebo; a control group with IV administration of 2.5 mg/kg of placebo prior to first graft reperfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PaO2/FiO2 ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen)	2 hours post-lung transplantation
PaO2/FiO2 ratio	6 hours post-lung transplantation
PaO2/FiO2 ratio	12 hours post-lung transplantation
PaO2/FiO2 ratio	18 hours post-lung transplantation
PaO2/FiO2 ratio	24 hours post-lung transplantation
PaO2/FiO2 ratio	36 hours post-lung transplantation
PaO2/FiO2 ratio	48 hours post-lung transplantation
PaO2/FiO2 ratio	60 hours post-lung transplantation
PaO2/FiO2 ratio	72 hours post-lung transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
primary graft failure grade	clinical status of primary graft failure at 72 hours	72 hours

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: François TRONC, Pr, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): September 1, 2018

Study Registration Dates

• First Submitted: August 18, 2016
• First Submitted That Met QC Criteria: August 18, 2016
• First Posted (Estimate): August 23, 2016

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: March 13, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Lung transplantation; Cyclosporine; Postconditioning
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 2013-816

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO