Naloxone for Optimizing Hypoxemia Of Lung Donors

Lung Transplantation Clinical Trial

— NO-HOLDS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02581111
• Other study ID #: ODRC-001
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 2015
• Est. completion date: September 25, 2017

Study information

• Verified date: July 2020
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 199
• Est. completion date: September 25, 2017
• Est. primary completion date: September 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Brain Death
• Lung Transplantation
• Organ Donors

Intervention

Drug:
• Naloxone
Naloxone 8-mg IV bolus
• Normal saline

Locations

Country	Name	City	State
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Oxygenation (P/F Ratio) From Baseline to Final Pre-recovery Arterial Blood Gas (ABG)	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	Baseline and at time of organ recovery, within 72 hours
Secondary	Number of Participants Who Had Lungs Transplanted	Whether one or both lungs were transplanted from this organ donor (dichotomized)	At time of organ recovery (within 72 hours)
Secondary	Acute Change in Oxygenation (P/F Ratio)	Change in PaO2:FiO2 ratio from ABG at 4-6 hours after randomization compared to baseline prior to randomization	Baseline and ABG at 4-6 hours after intervention