Opioid UsePhase 4OSPREyNCT03726268

Optimizing Outpatient Anesthesia (OSPREy-Outpatient Surgery Pain Relief Enhancement)

A Phase 4 study testing Methadone, Fentanyl and Hydromorphone in people with Opioid Use and Pain, Postoperative, run by Duke University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The overall goal of this research is to improve perioperative pain treatment, decrease post-operative opioid consumption, diminish opioid related side effects, and reduce postop opioid prescribing (and hence opportunity for diversion, abuse, addiction, and fatal overdose). Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Opioid Use, Pain, Postoperative
What is being tested?: Methadone, Fentanyl and Hydromorphone
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 907 participants
Where: 1 siteUnited States
Study dates: 29 Nov 2018to 30 Jan 2024
Phase: Phase 4
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 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18-65 years Undergoing general anesthesia and moderately painful ambulatory surgery with anticipated postop stay of < 24 hours
Signed, written, informed consent

Who cannot join

History of liver or kidney disease.
Females who are pregnant or nursing.
Chronic opioid use (e.g. preoperative daily use of methadone, fentanyl transdermal patches, or ≥ 3 oxycodone pills)

Trial locations and contacts

1 site in 1 country.

United States1 site

Duke University Medical Center
Durham, North Carolina, 27710

Other trials in United States

About this study

Read the detailed description

This protocol will test the innovative, paradigm-shifting hypothesis that anesthesia for outpatient surgery with long-duration opioids (methadone), compared with conventional short-duration opioids, achieves better analgesia, with similar or diminished side effects, may reduce development of chronic postsurgical pain, improves recovery, and importantly, decreases postoperative opioid consumption and could hence diminish take-home opioid prescribing and shrink the population reservoir of unused opioids available for diversion and misuse. Two cohorts will be studied, but analyzed separately. 1) Short-stay, anticipated next-day discharge surgery (compare short-duration vs long-duration opioid), 2) Same-day discharge surgery (compare short-duration vs long-duration opioid).

Conditions: Opioid Use, Pain, Postoperative
Being tested: Methadone, Fentanyl, Hydromorphone, Morphine, Sufentanil
Medical subject headings: Pain, Postoperative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MethadoneDrug
Dose is 0.15-0.3 mg/kg IV methadone HCl given intraoperatively and in the immediate post-operative period. Intraoperative methadone doses are 15 mg in "short-stay, anticipated next-day discharge" patients (10 mg if ≤55kg), and 10 mg in "same-day" surgery patients.
FentanylDrug
Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
HydromorphoneDrug
Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
MorphineDrug
Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).
SufentanilDrug
Given per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).

Study groups in NCT03726268
Study group	Role	What they receive
Short-stay, IV methadone	Active comparator	Anticipated next-day discharge; intraoperative and post-operative IV methadone Receives: Drug: Methadone
Short-stay, IV short-acting opioids	Active comparator	Anticipated next-day discharge; intraoperative and post-operative IV fentanyl, sufentanil, morphine, or hydromorphone at anesthesia provider discretion Receives: Drug: Fentanyl; Drug: Hydromorphone; Drug: Morphine; Drug: Sufentanil
Same-day, IV methadone	Active comparator	Intraoperative and post-operative IV methadone Receives: Drug: Methadone
Same-day, IV short-acting opioids	Active comparator	Intraoperative and post-operative IV fentanyl, sufentanil, morphine or hydromorphone at anesthesia provider discretion Receives: Drug: Fentanyl; Drug: Hydromorphone; Drug: Morphine; Drug: Sufentanil

What is being measured

The primary outcome is the main question the study is designed to answer.

Total 30 Day Post-discharge Home Opioid Use (Number of Tablets)
Based on home diary and hospital record. Number of opioid tablets from PACU discharge to postoperative day (POD) 30 for Same Day subjects, and number of opioid tablets from POD 1 to POD 30 for Short-Stay subjects.
Measured: Approximately 30 days

Secondary outcomes (4)

Total Intraoperative Non-methadone Opioid Administration
Based on hospital record.
Measured: Approximately 12 hours
Total Post Anesthesia Care Unit (PACU) Opioid Administration
Based on hospital record.
Measured: Approximately 2 hours
Total Hospital Non-methadone Opioid Administration
Based on hospital record.
Measured: Start of surgery to hospital discharge, up to 2 days
Total 7-day Post-PACU Discharge Home Opioid Use
Based on home diary and hospital record. Number of opioid tablets from PACU discharge to postoperative day (POD) 7 for Same Day subjects, and number of opioid tablets from POD 1 to POD 7 for Short-Stay subjects.
Measured: Up to 7 days post-PACU discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Nov 201830 Jan 2024

First posted31 Oct 2018
Study start29 Nov 2018
Primary completion30 Jul 2023
Study completion30 Jan 2024

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 Opioid UseStudies of the same condition, open and under way.
More trials run by Duke UniversityThe 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 907 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03726268
Sponsor's protocol ID: Pro00089977
Other IDs: 1R01DA042985-01
Acronym: OSPREy
Status last verified: Nov 2025
First submitted: 29 Oct 2018
Last updated: 19 Nov 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Kharasch ED, Schlabaugh C, Metzler E, Schultz A. Coronavirus Disease-2019 Pandemic Effects on Patient Decisions Regarding Clinical Trial Participation. Anesth Analg. 2024 Apr 1;138(4):906-908. doi: 10.1213/ANE.0000000000006783. Epub 2024 Mar 15. No abstract available.
PubMed 38447097

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 19 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Optimizing Outpatient Anesthesia (OSPREy-Outpatient Surgery Pain Relief Enhancement)
ClinicalTrials.gov ID: NCT03726268
Acronym / sponsor ID: OSPREy / Pro00089977
Conditions: Opioid Use, Pain, Postoperative
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 907 participants (actual)
Lead sponsor: Duke UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 29 Nov 2018 (actual)
Primary completion: 30 Jul 2023 (actual)
Study completion: 30 Jan 2024 (actual)
First posted: 31 Oct 2018 (actual)
Results: Posted 19 Nov 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Short-stay, IV methadone	Active comparator	Drug: MethadoneAnticipated next-day discharge; intraoperative and post-operative IV methadone
Short-stay, IV short-acting opioids	Active comparator	Drug: Fentanyl, Drug: Hydromorphone, Drug: Morphine, Drug: SufentanilAnticipated next-day discharge; intraoperative and post-operative IV fentanyl, sufentanil, morphine, or hydromorphone at anesthesia provider discretion
Same-day, IV methadone	Active comparator	Drug: MethadoneIntraoperative and post-operative IV methadone
Same-day, IV short-acting opioids	Active comparator	Drug: Fentanyl, Drug: Hydromorphone, Drug: Morphine, Drug: SufentanilIntraoperative and post-operative IV fentanyl, sufentanil, morphine or hydromorphone at anesthesia provider discretion

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Age 18-65 years Undergoing general anesthesia and moderately painful ambulatory surgery with anticipated postop stay of < 24 hours
Signed, written, informed consent

Key exclusion criteria (3 listed)

History of liver or kidney disease.
Females who are pregnant or nursing.
Chronic opioid use (e.g. preoperative daily use of methadone, fentanyl transdermal patches, or ≥ 3 oxycodone pills)

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
MethadoneDose is 0.15-0.3 mg/kg IV methadone HCl given intraoperatively and in the immediate post-operative period. Intraoperative methadone doses are 15 mg in "short-stay, anticipated next-day discharge" patients (10 mg if ≤55kg), and 10 mg in "same-day" surgery patients.	Drug	Same-day, IV methadone, Short-stay, IV methadone
FentanylGiven per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).	Drug	Same-day, IV short-acting opioids, Short-stay, IV short-acting opioids
HydromorphoneGiven per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).	Drug	Same-day, IV short-acting opioids, Short-stay, IV short-acting opioids
MorphineGiven per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).	Drug	Same-day, IV short-acting opioids, Short-stay, IV short-acting opioids
SufentanilGiven per clinical provider discretion intraoperatively and in the immediate post-operative period (while patient remains in the post anesthesia care unit (PACU)).	Drug	Same-day, IV short-acting opioids, Short-stay, IV short-acting opioids

Primary outcome

Total 30 Day Post-discharge Home Opioid Use (Number of Tablets)
Time frame: Approximately 30 days
Based on home diary and hospital record. Number of opioid tablets from PACU discharge to postoperative day (POD) 30 for Same Day subjects, and number of opioid tablets from POD 1 to POD 30 for Short-Stay subjects.

4 secondary outcomes

Total Intraoperative Non-methadone Opioid Administration
Time frame: Approximately 12 hours
Total Post Anesthesia Care Unit (PACU) Opioid Administration
Time frame: Approximately 2 hours
Total Hospital Non-methadone Opioid Administration
Time frame: Start of surgery to hospital discharge, up to 2 days
Total 7-day Post-PACU Discharge Home Opioid Use
Time frame: Up to 7 days post-PACU discharge

Results and safety

Results posted to the registry on 19 Nov 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Short-stay, IV Methadone	188	175
Short-stay, IV Short-acting Opioids	188	175
Same-day, IV Methadone	205	190
Same-day, IV Short-acting Opioids	205	194

Primary outcome: Total 30 Day Post-discharge Home Opioid Use (Number of Tablets)

Time frame: Approximately 30 days. Mean (Standard Deviation). Unit: tablets

Measure	Short-stay, IV Methadone n = 147	Short-stay, IV Short-acting Opioids n = 140	Same-day, IV Methadone n = 167	Same-day, IV Short-acting Opioids n = 161
Value	10.00 (15.50)	10.00 (11.60)	6.18 (8.40)	6.67 (10.40)

Short-stay, IV Methadone vs Short-stay, IV Short-acting Opioids: p = 0.970, Negative binomial regression
Same-day, IV Methadone vs Same-day, IV Short-acting Opioids: p = 0.631, Negative binomial regression

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Approximately 30 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Short-stay, IV Methadone	6 of 188 (3.2%)	21 of 188 (11.2%)	0 of 188
Short-stay, IV Short-acting Opioids	6 of 188 (3.2%)	17 of 188 (9%)	1 of 188
Same-day, IV Methadone	10 of 205 (4.9%)	29 of 205 (14.1%)	0 of 205
Same-day, IV Short-acting Opioids	11 of 205 (5.4%)	16 of 205 (7.8%)	0 of 205

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38447097Kharasch ED, Schlabaugh C, Metzler E, Schultz A. Coronavirus Disease-2019 Pandemic Effects on Patient Decisions Regarding Clinical Trial Participation. Anesth Analg. 2024 Apr 1;138(4):906-908. doi: 10.1213/ANE.0000000000006783. Epub 2024 Mar 15. No abstract available.

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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.

Evan Kharasch, MD principal investigator

Duke University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Methadone, Fentanyl and Hydromorphone in people with Opioid Use and Pain, Postoperative, run by Duke University at 1 site 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 2 inclusion and 3 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 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 19 Nov 2025). 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?

Total 30 Day Post-discharge Home Opioid Use (Number of Tablets) (time frame: Approximately 30 days). 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 NCT03726268, 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 19 Nov 2025.