Clinical trial NCT02581111: Naloxone for Optimizing Hypoxemia Of Lung Donors
Official title: Randomized Placebo-controlled Trial of Intravenous Naloxone to Improve Oxygenation in Hypoxemic Lung-Eligible Brain-Dead Organ Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Brain Death
Organ Donors
Lung Transplantation
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2015-10-20
Enrollment: 199
Sex: ALL
Minimum age (years): 13
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 (Organ Procurement Organization) management reveals hypoxemia, as defined by the ratio of partial pressure of oxygen in arterial blood (PaO2) to fraction of inspired oxygen (FiO2) below 300 mm Hg, 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 description: 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 (PFR - PaO2 divided by FiO2, on positive end-expiratory pressure \[PEEP\] 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.

Eligibility criteria: Inclusion Criteria:

* Brain-dead organ donor being managed by OPO (organ procurement organization)
* Lungs being considered for recovery and transplant
* Baseline ABG (after authorization) with P/F ratio \< 300

Exclusion Criteria:

* No authorization for research
* Lungs already excluded for transplant (e.g. known chronic obstructive pulmonary disease \[COPD\], human immunodeficiency virus \[HIV\] infection)

Primary outcomes:
measure: Change in Oxygenation (P/F Ratio) From Baseline to Final Pre-recovery Arterial Blood Gas (ABG)
timeFrame: Baseline and at time of organ recovery, within 72 hours
Secondary outcomes:
measure: Number of Participants Who Had Lungs Transplanted
timeFrame: At time of organ recovery (within 72 hours)
measure: Acute Change in Oxygenation (P/F Ratio)
timeFrame: Baseline and ABG at 4-6 hours after intervention
Other outcomes:
Locations:
city: Denver
country: United States
facility: Donor Alliance
state: Colorado
city: Metairie
country: United States
facility: Louisiana Organ Procurement Agency
state: Louisiana
city: Saint Louis
country: United States
facility: Mid-America Transplant Services
state: Missouri
city: Columbus
country: United States
facility: Lifeline of Ohio
state: Ohio
Study officials:
affiliation: Washington University School of Medicine
name: Rajat Dhar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dhar R, Stahlschmidt E, Paramesh A, Marklin G. A Randomized Controlled Trial of Naloxone for Optimization of Hypoxemia in Lung Donors After Brain Death. Transplantation. 2019 Jul;103(7):1433-1438. doi: 10.1097/TP.0000000000002511.