Brain DeathPhase 2/3NO-HOLDSNCT02581111
Naloxone for Optimizing Hypoxemia Of Lung Donors
A Phase 2/3 study testing Naloxone and Normal saline in people with Brain Death and Organ Donors, run by Washington University School of Medicine at 4 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 13 to 70 years
- Conditions the study is for
- Brain Death, Organ Donors, Lung Transplantation
- What is being tested?
- Naloxone and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 199 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2015to 25 Sep 2017
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- No authorization for research
- Lungs already excluded for transplant (e.g. known chronic obstructive pulmonary disease [COPD], human immunodeficiency virus [HIV] infection)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Lifeline of Ohio
Columbus, Ohio, 43212
Donor Alliance
Denver, Colorado, 80246
Louisiana Organ Procurement Agency
Metairie, Louisiana, 70002
Mid-America Transplant Services
St Louis, Missouri, 63110
About this study
Official title: Randomized Placebo-controlled Trial of Intravenous Naloxone to Improve Oxygenation in Hypoxemic Lung-Eligible Brain-Dead Organ Donors
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.
Read the 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
- Being tested
- Naloxone, Normal saline
- Medical subject headings
- Brain Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaloxoneDrug
Also called Narcan
Naloxone 8-mg IV bolus
Normal salineDrug
Also called saline
| Study group | Role | What they receive |
|---|---|---|
| Naloxone | Experimental | Naloxone 8-mg IV given once after baseline ABG Receives: Drug: Naloxone |
| Placebo | Sham comparator | Equivalent volume of saline given once Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and at time of organ recovery, within 72 hours
Secondary outcomes (2)
Number of Participants Who Had Lungs Transplanted
Whether one or both lungs were transplanted from this organ donor (dichotomized)
Measured: At time of organ recovery (within 72 hours)
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
Measured: Baseline and ABG at 4-6 hours after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2015 (estimated)
- Study startSep 2015
- Primary completion22 Sep 2017
- Study completion25 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain DeathStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raj Dhar, Washington University School of Medicine
- Investigators
- Rajat Dhar, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02581111
- Sponsor's protocol ID
- ODRC-001
- Acronym
- NO-HOLDS
- Status last verified
- Jul 2020
- First submitted
- 1 Oct 2015
- Last updated
- 31 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 30399122
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo-controlled Trial of Intravenous Naloxone to Improve Oxygenation in Hypoxemic Lung-Eligible Brain-Dead Organ Donors
- ClinicalTrials.gov ID
- NCT02581111
- Acronym / sponsor ID
- NO-HOLDS / ODRC-001
- Conditions
- Brain Death, Organ Donors, Lung Transplantation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 199 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Sep 2015 (actual)
- Primary completion
- 22 Sep 2017 (actual)
- Study completion
- 25 Sep 2017 (actual)
- First posted
- 20 Oct 2015 (estimated)
- Results
- Posted 16 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naloxone | Experimental | Drug: NaloxoneNaloxone 8-mg IV given once after baseline ABG |
| Placebo | Sham comparator | Drug: Normal salineEquivalent volume of saline given once |
Who may qualify
- Ages
- 13 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- No authorization for research
- Lungs already excluded for transplant (e.g. known chronic obstructive pulmonary disease [COPD], human immunodeficiency virus [HIV] infection)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaloxoneAlso: NarcanNaloxone 8-mg IV bolus | Drug | Naloxone |
| Normal salineAlso: saline | Drug | Placebo |
Primary outcome
Change in Oxygenation (P/F Ratio) From Baseline to Final Pre-recovery Arterial Blood Gas (ABG)
Time frame: 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
2 secondary outcomes
Number of Participants Who Had Lungs Transplanted
Time frame: At time of organ recovery (within 72 hours)
Acute Change in Oxygenation (P/F Ratio)
Time frame: Baseline and ABG at 4-6 hours after intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30399122Dhar 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rajat Dhar, MD principal investigator
Washington University School of Medicine
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Naloxone and Normal saline in people with Brain Death and Organ Donors, run by Washington University School of Medicine at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Oxygenation (P/F Ratio) From Baseline to Final Pre-recovery Arterial Blood Gas (ABG) (time frame: Baseline and at time of organ recovery, within 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02581111, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.