Clinical Trial: Repertaxin in Prevention of Primary Graft Dysfunction After Lung Transplantation

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Repertaxin in the Prevention of Primary Graft Dysfunction After Lung Transpl

Brief Summary: The chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after solid organ transplantation. Repertaxin is a novel, specific inhibitor of CXCL8. This study is configured to explore the safety and efficacy of repertaxin in preventing the primary graft dysfunction (PGD) after lung transplantation.

Detailed Summary: Lung transplantation has become a standard therapy for patients with end-stage lung disease. Within last decades, donor management, organ preservation, immunosuppressive regimens and control of infectious complications have been substantially improved. In addition, the operative techniques of transplantation procedures have been developed to an international standard of high quality. However, despite these refinements, significant reperfusion injury occurs in up to 10-20% of lung transplant recipients as the consequence of unavoidable processes of procurement, preservation and restoring blood flow. This clinical condition, recently termed primary graft dysfunction (PGD), remains an important problem after lung transplantation, and still represents the single biggest cause of early morbidity and mortality for lung recipients. In addition, there is some evidence to suggest a relationship between reperfusion injury, acute rejection, and the subsequent development of chronic graft dysfunction. In post-ischemia reperfusion, restoration of the blood supply (reperfusion) after prolonged tissue ischemia is associated with an inflammatory reaction characterized by massive polymorphonuclear neutrophil infiltration into the reperfused tissue. The infiltrating inflammatory cells can perpetuate the initial inflammatory reaction and induce further injuries. The importance of CXCL8 in lung tissue during the ischemic time and after reperfusion has been clearly demonstrated. The current standard of care in preventing this clinical condition focuses on prevention by way of surgical techniques in the procurement, storage and implantation of graft lungs. The efficacy of repertaxin in preventing polymorphonuclear neutrophil infiltration and tissue damage in rat models of kidney transplantation and lung transplantation, as well as the safety shown in human phase 1 studies, provide the rationale for a clinical study aimed at evaluating the effect of repertaxin in preventing PGD after lung
Sponsor: Dompé Farmaceutici S.p.A

Current Primary Outcome: PaO2/inspired oxygen fraction ratio on ICU admission and at 24 hours after ICU admission

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • PGD score
  • Time of mechanical ventilation
  • Duration of ICU stay
  • ICU mortality
  • Acute rejection episodes
  • Patient survival rate
  • Pharmacokinetic profile


Original Secondary Outcome: Same as current

Information By: Dompé Farmaceutici S.p.A

Dates:
Date Received: September 21, 2005
Date Started: May 2005
Date Completion:
Last Updated: November 26, 2008
Last Verified: November 2008