Postconditioning by Cyclosporin A in Pulmonary Transplantation

Overview

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 Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: September 2018

Interventions

  • Drug: Cyclosporine A
    • a pharmacological postconditioned group with IV administration of 2.5 mg/kg of CsA 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

Arms, Groups and Cohorts

  • Experimental: 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

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • primary graft failure grade
    • Time Frame: 72 hours
    • clinical status of primary graft failure at 72 hours

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Hospices Civils de Lyon
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Fran├žois TRONC, Pr, Principal Investigator, Hospices Civils de Lyon

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.