Hydromorphone UsePhase 4NCT02107339
Methadone and Hydromorphone For Spinal Surgery
A Phase 4 study testing Methadone and Hydromorphone in people with Hydromorphone Use and Acute Postoperative Pain, run by Endeavor Health at 1 site in United States.
Trial summary
Patients undergoing major spinal surgery continue to experience moderate-to-severe pain during the first 2-3 days following the operative procedure. Pain complicates the recovery process, despite the routine practice of using potent opioid analgesics. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hydromorphone Use, Acute Postoperative Pain, Patient Satisfaction
- What is being tested?
- Methadone and Hydromorphone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Sep 2017
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All patients presenting for elective posterior lumbar or thoracic spinal fusion surgery will be eligible for enrollment.
Who cannot join
- Preoperative renal failure (defined as a serum creatinine > 2.0 mg/dL.)
- American Society of Anesthesiologists Physical Status IV or V
- Pulmonary disease necessitating home oxygen therapy
- Allergy to methadone or hydromorphone
- Preoperative recent history of opioid or alcohol abuse
- Inability to use a PCA device or speak the English language
Trial locations and contacts
1 site in 1 country.
United States1 site
NorthShore University HealthSystem
Evanston, Illinois, 60201
About this study
Patients undergoing major spinal surgery continue to experience moderate-to-severe pain during the first 2-3 days following the operative procedure. Pain complicates the recovery process, despite the routine practice of using potent opioid analgesics. The primary reason that pain is poorly controlled in patients undergoing major surgery is that most commonly-used opioids only produce analgesia for 2-4 hours. The intermittent use of these drugs results in periods of time when a patient will experience discomfort (at which time a nurse administers more drug or the button on a patient-controlled analgesic (PCA) system is pressed to deliver more medication). The use of a long-acting opioid may be advantageous in the perioperative setting. Methadone is an opioid that has a median duration of analgesia of 24-36 hours. Therefore, a single dose administered in the operating room may reduce the need for pain medication and improve pain control for the first few postoperative days. The aim of this randomized clinical trial is to examine the effect of methadone (compared to hydromorphone) on postoperative pain management in patients undergoing major spine surgery
Read the detailed description
Patients: 100 patients (ages 18-80) will be enrolled in this clinical trial. All patients presenting for elective posterior lumbar or thoracic spinal fusion surgery will be eligible for enrollment. Patients will be randomized to receive either methadone or hydromorphone on the basis of a computer generated random number table. Patients in each group will receive standard clinical intraoperative doses of either methadone (0.2 mg/kg) or hydromorphone (2 mg). An analysis of patients undergoing posterior lumbar fusion surgery at Evanston Hospital revealed that patients received, on average, approximately 2 mg of hydromorphone intraoperatively. The most commonly used doses of methadone administered in clinical studies have been either 0.2 mg/kg or a dose of 20 mg. Furthermore, these doses also represent dosages which appear to be approximately equipotent. Study medications will be prepared by the pharmacy, and all clinicians will be blinded to group assignment. Two syringes will be prepared for each patient, one which contains the study drug (either methadone 0.2 mg/kg or hydromorphone 2 mg), and the other containing the placebo (saline). If the patient is randomized to the methadone group, a 3 cc syringe containing 0.2 mg/kg of methadone and saline (total volume 3 cc) will be prepared, as well as a 10 cc syringe containing 10 cc of saline (placebo). If the patient is randomized to the hydromorphone group, a 3 cc syringe containing 3 cc of saline (placebo) will be prepared, as well as a 10 cc syringe containing 2 mg of hydromorphone with 9 cc of saline (total volume 10 cc). At induction of anesthesia, the 3 cc syringe containing either 0.2 mg/kg of methadone or placebo will be given over 5 seconds. At the conclusion of surgery, the 10 cc syringe of either hydromorphone or placebo will be titrated slowly per clinician's preference. The administration of all other anesthetic agents will be standardized and reflect the usual practices of anesthesiologists at Evanston Hospital (spine protocol).
Anesthesia will be standardized and include propofol for induction, a propofol and remifentanil infusion for maintenance (plus sevoflurane), and IV acetaminophen 1000 mg during the last 60 minutes of the case.
On arrival to the postanesthesia care unit (PACU), patients will be assessed for pain by PACU nurses per standard protocols. Patients will be evaluated for pain on PACU arrival and then every 15 minutes. Patients will be administered hydromorphone 0.25-0.5 mg for pain, and doses will be repeated until the patient is comfortable (pain < 3 on a scale of 0-10; 0=no pain and 10=worst pain imaginable). The patient will then be connected to a PCA device to deliver pain medication during the remainder of the postoperative period.
All postoperative management will be per standard surgical protocols
Sample Size: The primary end-point of the investigation is amount of hydromorphone used. In a clinical trial by Urban et al. of patients undergoing complex spine surgery using a standard anesthetic, average hydromorphone consumption in the first 24 hours was 27 mg (18). The investigators expect to see at least a 33% reduction in hydromorphone consumption in the methadone group. Group sample sizes of 39 and 39 achieve 91% power to detect a difference of 9.0 between the null hypothesis that both group means are 27.0 and the alternative hypothesis that the mean of group 2 is 18.0 with estimated group standard deviations of 10.0 and 10.0 and with a significance level (alpha) of 0.01000 using a two-sided two-sample t-test. The investigators plan to enroll a total of 100 patients to ensure complete collection of data.
- Conditions
- Hydromorphone Use, Acute Postoperative Pain, Patient Satisfaction, Chronic Persistent Surgical Pain
- Being tested
- Methadone, Hydromorphone
- Keywords
- methadone, hydromorphone, acute postoperative pain, chronic persistent surgical pain
- Medical subject headings
- Pain, Postoperative, Patient Satisfaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Methadone 0.2 mg/kg administered at induction of anesthesia
HydromorphoneDrug
Hydromorphone 2 mg administered at the conclusion of anesthesia
| Study group | Role | What they receive |
|---|---|---|
| methadone group | Experimental | Patient will receive methadone 0.2 mg/kg at induction of anesthesia (single dose) Receives: Drug: Methadone |
| Hydromorphone group | Active comparator | Patients will receive hydromorphone 2 mg at the end of the surgical procedure Receives: Drug: Hydromorphone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hydromorphone Use at 24 Hours
Measured: Use of hydromorphone at 24 hours
Secondary outcomes (15)
Hydromorphone Use Second 24 Hours
Measured: 24-48 hours after surgery
Hydromorphone Use Third 24 Hours
Measured: 48-72 hours after surgery
Pain Scores Postanesthesia Care Unit (PACU) Arrival
11-point verbal rating scale (0=no pain, 10=worst pain imaginable)
Measured: First 5 minutes after PACU arrival
Pain Scores 1 Hour After PACU Arrival
11-point verbal rating scale (0=no pain, 10=worst pain imaginable)
Measured: Pain scores at 60 minutes after PACU admission
Pain Scores 2 Hours After PACU Arrival
11-point verbal rating scale (0=no pain, 10=worst pain imaginable)
Measured: Pain scores at 120 minutes after PACU admission
Pain Scores on Postoperative Day One
11-point verbal rating scale (0=no pain, 10=worst pain imaginable)
Measured: Pain scores one day after PACU admission
Pain Scores on Postoperative Day 2
11-point verbal rating scale (0=no pain, 10=worst pain imaginable)
Measured: Pain scores 48 hours after PACU admission
Pain Scores Postoperative Day 3
11-point verbal rating scale (0=no pain, 10=worst pain imaginable)
Measured: Pain scores 72 hours after PACU admission
Patient Satisfaction Scores
Patient satisfaction with overall pain management will be determined using a 101-point verbal rating scale (0=highly dissatisfied (worst), 100=highly satisfied (best))
Measured: Postopertive day 1
Patient Satisfaction Scores
Patient satisfaction with overall pain management will be determined using a 101-point verbal rating scale (0=highly dissatisfied (worst), 100=highly satisfied (best))
Measured: postoperative day 2
Patient Satisfaction Scores
Patient satisfaction with overall pain management will be determined using a 101-point verbal rating scale (0=highly dissatisfied (worst), 100=highly satisfied (best))
Measured: Postoperative day 3
Chronic Persistent Surgical Pain-Weekly Frequency of Pain
0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant
Measured: One month after surgery
Chronic Persistent Surgical Pain-weekly Frequency of Pain
0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant
Measured: 3 months after surgery
Chronic Persistent Surgical Pain-Weekly Frequency of Pain
0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant
Measured: 6 months after surgery
Chronic Persistent Surgical Pain-Weekly Frequency of Pain
0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant
Measured: 12 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study startMar 2014
- Primary completionJul 2016
- Study completionSep 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.
- Other trials for Hydromorphone UseStudies of the same condition, open and under way.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endeavor Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Glenn Murphy, Endeavor Health
- Investigators
- Glenn S Murphy, MD, Principal investigator, Endeavor Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02107339
- Sponsor's protocol ID
- EH14-113
- Status last verified
- Sep 2019
- First submitted
- 4 Apr 2014
- Last updated
- 30 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methadone and Hydromorphone For Spinal Surgery
- ClinicalTrials.gov ID
- NCT02107339
- Acronym / sponsor ID
- EH14-113
- Conditions
- Hydromorphone Use, Acute Postoperative Pain, Patient Satisfaction, Chronic Persistent Surgical Pain
- Keywords
- methadone, hydromorphone, acute postoperative pain, chronic persistent surgical pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Endeavor HealthUniversity, hospital or other
- Study start
- Mar 2014 (actual)
- Primary completion
- Jul 2016 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 8 Apr 2014 (estimated)
- Results
- Posted 16 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients undergoing major spinal surgery continue to experience moderate-to-severe pain during the first 2-3 days following the operative procedure. Pain complicates the recovery process, despite the routine practice of using potent opioid analgesics. The primary reason that pain is poorly controlled in patients undergoing major surgery is that most commonly-used opioids only produce analgesia for 2-4 hours. The intermittent use of these drugs results in periods of time when a patient will experience discomfort (at which time a nurse administers more drug or the button on a patient-controlled analgesic (PCA) system is pressed to deliver more medication). The use of a long-acting opioid may be advantageous in the perioperative setting. Methadone is an opioid that has a median duration of analgesia of 24-36 hours. Therefore, a single dose administered in the operating room may reduce the need for pain medication and improve pain control for the first few postoperative days. The aim of this randomized clinical trial is to examine the effect of methadone (compared to hydromorphone) on postoperative pain management in patients undergoing major spine surgery
Detailed description
Patients: 100 patients (ages 18-80) will be enrolled in this clinical trial. All patients presenting for elective posterior lumbar or thoracic spinal fusion surgery will be eligible for enrollment. Patients will be randomized to receive either methadone or hydromorphone on the basis of a computer generated random number table. Patients in each group will receive standard clinical intraoperative doses of either methadone (0.2 mg/kg) or hydromorphone (2 mg). An analysis of patients undergoing posterior lumbar fusion surgery at Evanston Hospital revealed that patients received, on average, approximately 2 mg of hydromorphone intraoperatively. The most commonly used doses of methadone administered in clinical studies have been either 0.2 mg/kg or a dose of 20 mg. Furthermore, these doses also represent dosages which appear to be approximately equipotent. Study medications will be prepared by the pharmacy, and all clinicians will be blinded to group assignment. Two syringes will be prepared for each patient, one which contains the study drug (either methadone 0.2 mg/kg or hydromorphone 2 mg), and the other containing the placebo (saline). If the patient is randomized to the methadone group, a 3 cc syringe containing 0.2 mg/kg of methadone and saline (total volume 3 cc) will be prepared, as well as a 10 cc syringe containing 10 cc of saline (placebo). If the patient is randomized to the hydromorphone group, a 3 cc syringe containing 3 cc of saline (placebo) will be prepared, as well as a 10 cc syringe containing 2 mg of hydromorphone with 9 cc of saline (total volume 10 cc). At induction of anesthesia, the 3 cc syringe containing either 0.2 mg/kg of methadone or placebo will be given over 5 seconds. At the conclusion of surgery, the 10 cc syringe of either hydromorphone or placebo will be titrated slowly per clinician's preference. The administration of all other anesthetic agents will be standardized and reflect the usual practices of anesthesiologists at Evanston Hospital (spine protocol).
Anesthesia will be standardized and include propofol for induction, a propofol and remifentanil infusion for maintenance (plus sevoflurane), and IV acetaminophen 1000 mg during the last 60 minutes of the case.
On arrival to the postanesthesia care unit (PACU), patients will be assessed for pain by PACU nurses per standard protocols. Patients will be evaluated for pain on PACU arrival and then every 15 minutes. Patients will be administered hydromorphone 0.25-0.5 mg for pain, and doses will be repeated until the patient is comfortable (pain < 3 on a scale of 0-10; 0=no pain and 10=worst pain imaginable). The patient will then be connected to a PCA device to deliver pain medication during the remainder of the postoperative period.
All postoperative management will be per standard surgical protocols
Sample Size: The primary end-point of the investigation is amount of hydromorphone used. In a clinical trial by Urban et al. of patients undergoing complex spine surgery using a standard anesthetic, average hydromorphone consumption in the first 24 hours was 27 mg (18). The investigators expect to see at least a 33% reduction in hydromorphone consumption in the methadone group. Group sample sizes of 39 and 39 achieve 91% power to detect a difference of 9.0 between the null hypothesis that both group means are 27.0 and the alternative hypothesis that the mean of group 2 is 18.0 with estimated group standard deviations of 10.0 and 10.0 and with a significance level (alpha) of 0.01000 using a two-sided two-sample t-test. The investigators plan to enroll a total of 100 patients to ensure complete collection of data.
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 |
|---|---|---|
| methadone group | Experimental | Drug: MethadonePatient will receive methadone 0.2 mg/kg at induction of anesthesia (single dose) |
| Hydromorphone group | Active comparator | Drug: HydromorphonePatients will receive hydromorphone 2 mg at the end of the surgical procedure |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients presenting for elective posterior lumbar or thoracic spinal fusion surgery will be eligible for enrollment.
Key exclusion criteria (6 listed)
- Preoperative renal failure (defined as a serum creatinine > 2.0 mg/dL.)
- American Society of Anesthesiologists Physical Status IV or V
- Pulmonary disease necessitating home oxygen therapy
- Allergy to methadone or hydromorphone
- Preoperative recent history of opioid or alcohol abuse
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 |
|---|---|---|
| MethadoneMethadone 0.2 mg/kg administered at induction of anesthesia | Drug | methadone group |
| HydromorphoneHydromorphone 2 mg administered at the conclusion of anesthesia | Drug | Hydromorphone group |
Primary outcome
Hydromorphone Use at 24 Hours
Time frame: Use of hydromorphone at 24 hours
15 secondary outcomes
Hydromorphone Use Second 24 Hours
Time frame: 24-48 hours after surgery
Hydromorphone Use Third 24 Hours
Time frame: 48-72 hours after surgery
Pain Scores Postanesthesia Care Unit (PACU) Arrival
Time frame: First 5 minutes after PACU arrival
Pain Scores 1 Hour After PACU Arrival
Time frame: Pain scores at 60 minutes after PACU admission
Pain Scores 2 Hours After PACU Arrival
Time frame: Pain scores at 120 minutes after PACU admission
Pain Scores on Postoperative Day One
Time frame: Pain scores one day after PACU admission
Pain Scores on Postoperative Day 2
Time frame: Pain scores 48 hours after PACU admission
Pain Scores Postoperative Day 3
Time frame: Pain scores 72 hours after PACU admission
Patient Satisfaction Scores
Time frame: Postopertive day 1
Patient Satisfaction Scores
Time frame: postoperative day 2
Patient Satisfaction Scores
Time frame: Postoperative day 3
Chronic Persistent Surgical Pain-Weekly Frequency of Pain
Time frame: One month after surgery
Chronic Persistent Surgical Pain-weekly Frequency of Pain
Time frame: 3 months after surgery
Chronic Persistent Surgical Pain-Weekly Frequency of Pain
Time frame: 6 months after surgery
Chronic Persistent Surgical Pain-Weekly Frequency of Pain
Time frame: 12 months after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Glenn S Murphy, MD principal investigator
Endeavor Health
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 and Hydromorphone in people with Hydromorphone Use and Acute Postoperative Pain, run by Endeavor Health 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 1 inclusion and 6 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 30 Sep 2019. 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 16 Aug 2016). 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?
Hydromorphone Use at 24 Hours (time frame: Use of hydromorphone at 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Sep 2019.