Clinical Trial: Naloxone for Optimizing Hypoxemia Of Lung Donors

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Randomized Placebo-controlled Trial of Intravenous Naloxone to Improve Oxygenation in Hypoxemic Lung-Eligible Brain-Dead Organ Donors

Brief Summary: Brain-dead patients who provide authorization for organ donation will be randomized to naloxone or placebo if baseline arterial blood gas (ABG, after initiation of OPO management) reveals hypoxemia (PF ratio < 300), unless they have already been ruled-out for lung recovery. Investigators aim to assess whether naloxone improves oxygenation prior to organ recovery more than placebo.

Detailed Summary: Naloxone has been used by many OPOs for decades to improve the pulmonary status of brain-dead organ donors (based on anecdotal evidence and small uncontrolled studies). Its efficacy in this population has never been assessed in a controlled clinical trial. The rationale for its use appears to be that it blocks the increase in capillary permeability that occurs with herniation and brain death (as demonstrated in a single sheep study of herniation). Investigators aim to rigorously test this hypothesis in a randomized placebo-controlled trial in brain-dead organ donors who have baseline hypoxemia. The primary outcome will be the acute change in oxygenation (on first follow-up ABG after naloxone as well as the final ABG prior to organ recovery). Investigators will also assess whether treatment results in more lungs being recovered and transplanted, after correcting for baseline variables such as age, blood group, smoking history, and cause of death. This study will be performed under the auspices of the Organ Donation Research Consortium and be carried out by multiple OPOs across the country. Naloxone or blinded placebo (identical syringe filled with saline) will be given after the baseline ABG shows hypoxemia (P/F ratio - the PaO2 divided by FiO2, on PEEP of 5 and usually 100% FiO2). Naloxone and placebo will both be co-administered with a neuromuscular blocking agent (e.g. vecuronium, per center protocol) to obviate any increase in spinal reflex movements that may be potentiated by naloxone treatment. All other protocols for organ donor management should be maintained at each OPO and no other study interventions are required. Transplant centers will be informed (through DonorNet) that the organ donor being considered for lung recovery has been enrolled in this blinded clinical trial.
Sponsor: Washington University School of Medicine

Current Primary Outcome: Change in oxygenation (P/F ratio) from baseline to final pre-recovery ABG [ Time Frame: within 72 hours, at time of organ recovery ]

Final ABG performed before organ recovery


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Lungs transplanted (yes/no) [ Time Frame: At time of organ recovery (within 72 hours) ]
    Whether one or both lungs were transplanted from this organ donor (dichotomized)
  • Acute change in oxygenation (P/F ratio) [ Time Frame: ABG at 4-6 hours after intervention ]


Original Secondary Outcome: Same as current

Information By: Washington University School of Medicine

Dates:
Date Received: October 1, 2015
Date Started: September 2015
Date Completion: June 30, 2017
Last Updated: May 8, 2017
Last Verified: May 2017