NO-HOLDS: Naloxone for Optimizing Hypoxemia Of Lung Donors
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2/Phase 3 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Naloxone Naloxone 8-mg IV given once after baseline ABG |
Drug: Naloxone
Naloxone 8-mg IV bolus
Other Names:
|
Sham Comparator: Placebo Equivalent volume of saline given once |
Drug: Normal saline
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
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)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Donor Alliance | Denver | Colorado | United States | 80246 |
2 | Louisiana Organ Procurement Agency | Metairie | Louisiana | United States | 70002 |
3 | Mid-America Transplant Services | Saint Louis | Missouri | United States | 63110 |
4 | Lifeline of Ohio | Columbus | Ohio | United States | 43212 |
Sponsors and Collaborators
- Washington University School of Medicine
Investigators
- Principal Investigator: Rajat Dhar, MD, Washington University School of Medicine
Study Documents (Full-Text)
More Information
Publications
None provided.- ODRC-001
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Naloxone | Placebo |
---|---|---|
Arm/Group Description | Naloxone 8-mg IV given once after baseline ABG Naloxone: Naloxone 8-mg IV bolus | Equivalent volume of saline given once Normal saline |
Period Title: Overall Study | ||
STARTED | 98 | 101 |
COMPLETED | 96 | 94 |
NOT COMPLETED | 2 | 7 |
Baseline Characteristics
Arm/Group Title | Naloxone | Placebo | Total |
---|---|---|---|
Arm/Group Description | Naloxone 8-mg IV given once after baseline ABG Naloxone: Naloxone 8-mg IV bolus | Equivalent volume of saline given once Normal saline | Total of all reporting groups |
Overall Participants | 98 | 101 | 199 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
37.4
(13)
|
36.8
(13)
|
37
(13)
|
Sex: Female, Male (Count of Participants) | |||
Female |
40
40.8%
|
50
49.5%
|
90
45.2%
|
Male |
58
59.2%
|
51
50.5%
|
109
54.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
5
5.1%
|
13
12.9%
|
18
9%
|
Not Hispanic or Latino |
87
88.8%
|
83
82.2%
|
170
85.4%
|
Unknown or Not Reported |
6
6.1%
|
5
5%
|
11
5.5%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
15
15.3%
|
20
19.8%
|
35
17.6%
|
White |
77
78.6%
|
76
75.2%
|
153
76.9%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
6
6.1%
|
5
5%
|
11
5.5%
|
Region of Enrollment (participants) [Number] | |||
United States |
98
100%
|
101
100%
|
199
100%
|
Outcome Measures
Title | Change in Oxygenation (P/F Ratio) From Baseline to Final Pre-recovery Arterial Blood Gas (ABG) |
---|---|
Description | 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 |
Time Frame | Baseline and at time of organ recovery, within 72 hours |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Naloxone | Placebo |
---|---|---|
Arm/Group Description | Naloxone 8-mg IV given once after baseline ABG Naloxone: Naloxone 8-mg IV bolus | Equivalent volume of saline given once Normal saline |
Measure Participants | 96 | 94 |
Median (Inter-Quartile Range) [mm Hg] |
81
|
80
|
Title | Number of Participants Who Had Lungs Transplanted |
---|---|
Description | Whether one or both lungs were transplanted from this organ donor (dichotomized) |
Time Frame | At time of organ recovery (within 72 hours) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Naloxone | Placebo |
---|---|---|
Arm/Group Description | Naloxone 8-mg IV given once after baseline ABG Naloxone: Naloxone 8-mg IV bolus | Equivalent volume of saline given once Normal saline |
Measure Participants | 98 | 101 |
Count of Participants [Participants] |
19
19.4%
|
19
18.8%
|
Title | Acute Change in Oxygenation (P/F Ratio) |
---|---|
Description | Change in PaO2:FiO2 ratio from ABG at 4-6 hours after randomization compared to baseline prior to randomization |
Time Frame | Baseline and ABG at 4-6 hours after intervention |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Naloxone | Placebo |
---|---|---|
Arm/Group Description | Naloxone 8-mg IV given once after baseline ABG Naloxone: Naloxone 8-mg IV bolus | Equivalent volume of saline given once Normal saline |
Measure Participants | 98 | 101 |
Median (Inter-Quartile Range) [mm Hg] |
71
|
33
|
Adverse Events
Time Frame | Till organ recovery (maximum of three days) | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Naloxone | Placebo | ||
Arm/Group Description | Naloxone 8-mg IV given once after baseline ABG Naloxone: Naloxone 8-mg IV bolus | Equivalent volume of saline given once Normal saline | ||
All Cause Mortality |
||||
Naloxone | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/98 (0%) | 0/101 (0%) | ||
Serious Adverse Events |
||||
Naloxone | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/98 (0%) | 0/101 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Naloxone | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/98 (0%) | 0/101 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Rajat Dhar |
---|---|
Organization | Washington University in St. Louis School of Medicine |
Phone | 3143622999 |
dharr@neuro.wustl.edu |
- ODRC-001