Postconditioning by Cyclosporin A in Pulmonary Transplantation

Lung Transplantation Clinical Trial

— CsA Poumon  

Official title:

Postconditioning by Cyclosporin A in Pulmonary Transplantation

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02876250
• Other study ID #: 2013-816
• Status: Withdrawn
• Phase: Phase 3
• Start date: January 2017
• Est. completion date: September 2018

Study information

• Verified date: March 2019
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Transplantation

Intervention

Drug:
• Cyclosporine A
a pharmacological postconditioned group with IV administration of 2.5 mg/kg of CsA prior to first graft reperfusion
• Placebo
a control group with IV administration of 2.5 mg/kg of placebo prior to first graft reperfusion

Locations

Country	Name	City	State
France	Hôpital Louis Pradel	Bron

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PaO2/FiO2 ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen)		2 hours post-lung transplantation
Primary	PaO2/FiO2 ratio		6 hours post-lung transplantation
Primary	PaO2/FiO2 ratio		12 hours post-lung transplantation
Primary	PaO2/FiO2 ratio		18 hours post-lung transplantation
Primary	PaO2/FiO2 ratio		24 hours post-lung transplantation
Primary	PaO2/FiO2 ratio		36 hours post-lung transplantation
Primary	PaO2/FiO2 ratio		48 hours post-lung transplantation
Primary	PaO2/FiO2 ratio		60 hours post-lung transplantation
Primary	PaO2/FiO2 ratio		72 hours post-lung transplantation
Secondary	primary graft failure grade	clinical status of primary graft failure at 72 hours	72 hours