NCT02876250

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jan 2017

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 18, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 23, 2016

Completed
4 months until next milestone

Study Start

First participant enrolled

January 1, 2017

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2018

Completed
Last Updated

March 14, 2019

Status Verified

March 1, 2019

Enrollment Period

1.7 years

First QC Date

August 18, 2016

Last Update Submit

March 13, 2019

Conditions

Lung Transplantation

Keywords

Lung transplantationCyclosporinePostconditioning

Outcome Measures

Primary Outcomes (9)

  • 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 Outcomes (1)

  • primary graft failure grade

    72 hours

Study Arms (2)

Cyclosporine A

EXPERIMENTAL

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

Drug: Cyclosporine A

Control

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Cyclosporine ADRUG

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

Cyclosporine A
PlaceboDRUG

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

Control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • No contra-indication to CsA administration.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hôpital Louis Pradel

Bron, France

Location

MeSH Terms

Interventions

Cyclosporine

Intervention Hierarchy (Ancestors)

CyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and Proteins

Study Officials

  • François TRONC, Pr

    Hospices Civils de Lyon

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 18, 2016

First Posted

August 23, 2016

Study Start

January 1, 2017

Primary Completion

September 1, 2018

Study Completion

September 1, 2018

Last Updated

March 14, 2019

Record last verified: 2019-03

Data Sharing

IPD Sharing
Will not share

Locations

FR(1)