Naloxone for Optimizing Hypoxemia Of Lung Donors

Phase 2

Completed

• Conditions: Lung Transplantation; Brain Death; Organ Donors
• Interventions: Drug: Naloxone; Drug: Normal saline

• Registration Number: NCT02581111
• Lead Sponsor: Washington University School of Medicine

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.

Study Timeline

• Study Start: 2015-09
• Study First Submitted: 2015-10-01
• Study First Submitted QC: 2015-10-19
• Study First Posted: 2015-10-20
• Primary Completion: 2017-09-22
• Study Completion: 2017-09-25
• Results First Submitted: 2018-08-20
• Results First Submitted QC: 2018-09-19
• Results First Posted: 2018-10-16
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-16
• Last Update Posted: 2020-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 199

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Naloxone	Naloxone	Naloxone 8-mg IV given once after baseline ABG
Placebo	Normal saline	Equivalent volume of saline given once

Primary Outcome Measures

Name	Time	Method
Change in Oxygenation (P/F Ratio) From Baseline to Final Pre-recovery Arterial Blood Gas (ABG)	Baseline and at time of organ recovery, within 72 hours	Change in ratio of partial pressure of oxygen in arterial blood (PaO2) to fraction of inspired oxygen (FiO2) from final ABG performed before organ recovery compared to baseline ABG

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Had Lungs Transplanted	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)	Baseline and ABG at 4-6 hours after intervention	Change in PaO2:FiO2 ratio from ABG at 4-6 hours after randomization compared to baseline prior to randomization

Trial Locations

Locations (4)

Lifeline of Ohio; 🇺🇸 Columbus, Ohio, United States

Donor Alliance; 🇺🇸 Denver, Colorado, United States

Louisiana Organ Procurement Agency; 🇺🇸 Metairie, Louisiana, United States

Mid-America Transplant Services; 🇺🇸 Saint Louis, Missouri, United States