Naloxone for Optimizing Hypoxemia Of Lung Donors

NCT ID: NCT02581111

Last Updated: 2020-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 199 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-09-25

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.

Conditions

Brain Death; Organ Donors; Lung Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Naloxone

Naloxone 8-mg IV given once after baseline ABG

Group Type: EXPERIMENTAL

Naloxone

Intervention Type: DRUG

Naloxone 8-mg IV bolus

Placebo

Equivalent volume of saline given once

Group Type: SHAM_COMPARATOR

Normal saline

Intervention Type: DRUG

Interventions

Naloxone

Naloxone 8-mg IV bolus

Intervention Type: DRUG

Normal saline

Intervention Type: DRUG

Other Intervention Names

Narcan; saline

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)

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Raj Dhar

Associate Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rajat Dhar, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Donor Alliance

Denver, Colorado, United States

Louisiana Organ Procurement Agency

Metairie, Louisiana, United States

Mid-America Transplant Services

St Louis, Missouri, United States

Lifeline of Ohio

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 30399122 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ODRC-001

Identifier Type: -

Identifier Source: org_study_id