Clinical Trial: Sodium Nitrite in Lung Transplant Patients to Minimize the Risk of Pulmonary Graft Dysfunction

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Sodium Nitrite Administration at the Time of Lung Organ Procurement and Transplantation to Minimize the Risk of Pulmonary Graft Dysfunction

Brief Summary: This is a Phase IIA observational nonrandomized pilot investigation to evaluate the safety and efficacy of Sodium Nitrite administration for the reduction of PGD in patients undergoing lung transplant. The study will enroll 8 subjects, undergoing lung transplant at the University of Pittsburgh Medical Center (UPMC).

Detailed Summary:

While increasing numbers of patients with advanced lung disease are candidates for lung transplantation, the short- and long-term outcomes are severely compromised by graft dysfunction, primarily in the form of organ rejection. The earliest manifestation of lung allograft dysfunction, termed primary graft dysfunction (PGD), represents a form of ischemia-reperfusion acute lung injury, and occurs in its severest form (Grade 3) in from 10 to 35% of lung transplant recipients 1-6. PGD is the primary cause of early morbidity and mortality after transplantation and is strongly associated with the late development of chronic lung rejection or Bronchiolitis Obliterans Syndrome (BOS. Early graft dysfunction contributes significantly to the suboptimal outcomes of lung transplantation and to the failure of lung transplant recipients to achieve five-year survival rates comparable to patients who receive other solid organs such as the heart and liver. The risk of PGD further limits the time that lungs can be stored ex-vivo, therefore restricting the pool of available donors. A critical advance in the prevention of both early and late lung allograft dysfunction will occur if PGD can be successfully prevented or minimized.

In this study, the investigators propose to test the hypothesis that administration of Sodium Nitrite to donor lungs and lung transplant recipients at the time of transplantation will be safe and will reduce the incidence of grades 2 and 3 PGD, thereby improving clinical outcomes with minimal toxicity.

Sodium Nitrite will be obtained from a commercial preparation (Hope Pharmaceuticals, Sodium Nitrite Injection USP (30mg/mL) NDC Number 60267-079-02) and the UPMC Pharmacy will prepare the formulations, which will be infused at three time points. First it will be infused into the preservation solution bag at the time of o
Sponsor: University of Pittsburgh

Current Primary Outcome: Incidence of grades 2+3 PGD grade during the first 72 hours post organ reperfusion. [ Time Frame: First 72 hours post organ reperfusion. ]

The primary study endpoint is the incidence of grades 2+3 PGD based upon the worst PGD grade during the first 72 hours post organ reperfusion (T0-72 or D0-D3).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of Methemoglobinemia during Nitrite infusion to the transplant [ Time Frame: 5, 30, and 60 minutes during the infusion; and at 5, 10, 30, 60, 90, 150 after the infusion. ]
    The safety of Sodium Nitrite administration will be assessed by measurement of methemoglobin levels during and after the nitrite infusion in the transplant recipient.
  • Incidence of fall in patient's mean arterial pressure greater than 20% from recorded baseline requiring discontinuation of drug infusion. [ Time Frame: Monitored at 1 minute intervals during study drug infusion followed by 15 minute intervals for 1 hour. ]
    The safety of Sodium Nitrite administration will be assessed by change in mean arterial pressure greater than 20% from recorded baseline during and after the nitrite infusion in the transplant recipient.
  • Incidence of acute and Chronic rejection [ Time Frame: Up to 12 months post Lung transplan ]
    To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of acute and chronic rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.


Original Secondary Outcome: Same as current

Information By: University of Pittsburgh

Dates:
Date Received: October 8, 2012
Date Started: October 2011
Date Completion: December 2017
Last Updated: September 26, 2016
Last Verified: September 2016