Repertaxin in Prevention of Primary Graft Dysfunction After Lung Transplantation

Lung Transplantation Clinical Trial

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 Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00224406
• Other study ID #: REP0104
• Status: Completed
• Phase: Phase 2
• First received: September 21, 2005
• Last updated: November 26, 2008
• Start date: May 2005
• Est. completion date: May 2008

Study information

• Verified date: November 2008
• Source: Dompé Farmaceutici S.p.A
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

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 transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 2008
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients accepted and listed for transplantation due to irreversible, progressive disabling, end-stage pulmonary disease

• Body weight 30 - 95 kg, inclusive (i.e. up to 95.99 kg)

• Planned isolated (single and bi-lateral) lung transplant from a non-living donor with brain death

• Normal renal function at the time of transplant

• Patient willing and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations

• Patient given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

Exclusion Criteria:

• Recipients of an intended multiple organ transplant, including heart-lung and liver-lung transplantation

• Recipients of a lung from a living lobar donor

• Recipients of a lung from a non-heart beating donor

• Re-do lung transplantation

• Recipients requiring mechanical ventilation at the time of transplant

• Recipients with extra-respiratory tract site of infection

• Recipients with hepatic dysfunction at the time of transplant

• Hypersensitivity to ibuprofen or to more than one non steroidal anti-inflammatory drug (NSAID)

• Hypersensitivity to medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib

• Patients simultaneously participating in any other studies involving a study drug to be administered concomitantly with the Investigational Product and/or a study drug intended to prevent ischemia/reperfusion injury

• Planned use of anti-CD3 monoclonal antibody (Orthoclone OKT3) or alemtuzumab (Campath) induction immunosuppression

• Planned use of sirolimus in the first three months after transplantation

• Pregnant or breast-feeding women

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Ischemia-Reperfusion Injury
• Lung Transplantation
• Primary Graft Dysfunction
• Reperfusion Injury

Intervention

Drug:
• repertaxin

Locations

Country	Name	City	State
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Colorado, Health Sciences Centre	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	University of South California, Department of Cardiothoracic Surgery	Los Angeles	California
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Dompé Farmaceutici S.p.A

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PaO2/inspired oxygen fraction ratio on ICU admission and at 24 hours after ICU admission
Secondary	PGD score
Secondary	Time of mechanical ventilation
Secondary	Duration of ICU stay
Secondary	ICU mortality
Secondary	Acute rejection episodes
Secondary	Patient survival rate
Secondary	Pharmacokinetic profile