Pain, PostoperativePhase 4NCT01542645
The Effect of Choice of Intraoperative Opioid on Postoperative Pain
A Phase 4 study testing Methadone and Fentanyl in people with Pain, Postoperative and Chronic Pain, run by Endeavor Health at 1 site in United States.
Trial summary
The primary aim of this randomized, double-blind study is to examine the effect of a single intraoperative dose of methadone on postoperative pain and analgesic requirements in patients undergoing cardiac surgery with cardiopulmonary bypass. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Pain, Postoperative, Chronic Pain
- What is being tested?
- Methadone and Fentanyl
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Sep 2014
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients presenting for elective cardiac surgery with CPB will be eligible for enrollment.
Who cannot join
- Preoperative renal failure requiring dialysis
- Significant hepatic dysfunction (liver function tests > 2 times upper normal limit)
- Preoperative ejection fraction < 30%
- Pulmonary disease necessitating home oxygen therapy
- Preoperative requirement for inotropic agents or intraaortic balloon pump to maintain hemodynamic stability
- Allergy to methadone or fentanyl
- Preoperative pain, use of preoperative opioids, or recent history of opioid abuse
Trial locations and contacts
1 site in 1 country.
United States1 site
NorthShore University HealthSystem
Evanston, Illinois, 60201
About this study
The primary aim of this randomized, double-blind study is to examine the effect of a single intraoperative dose of methadone on postoperative pain and analgesic requirements in patients undergoing cardiac surgery with cardiopulmonary bypass. These patients will be compared to subjects receiving a standard dose of the "traditional" intraoperative opioid (fentanyl). Secondary outcome measures to be assessed will include standard recovery variables (such as length of postoperative intubation, ICU length of stay, incidence of nausea or vomiting, level of sedation). In addition, patients will be assessed for the development of chronic postoperative pain.
Read the detailed description
Patients will be randomized to receive either methadone or fentanyl on the basis of a computer generated random number table. Patients in each group will receive standard intraoperative doses of either methadone or fentanyl that will allow for early tracheal extubation (within 4-8 hours of the conclusion of the surgical procedure). Study infusions will be prepared by the pharmacy, and all clinicians will be blinded to group assignment (methadone group-0.3 mg/kg-100 mL normal saline; fentanyl group-12 μg/kg-100 mL normal saline).
Pain will be assessed by blinded observers using a 11-point verbal analogue scale (0=no pain, 10=worst pain imaginable). Assessment for pain will be performed 15 minutes post-extubation and then 2, 4, 8, 12, 24, 48, and 72 hours after tracheal extubation. Pain will be determined at rest, with coughing, and during movement. At the same time pain data is collected, several other clinical assessments will be completed. The presence or absence of nausea and vomiting will be determined, and severity quantified using a 4-point ordinal scale (0=none, 3=severe). Level of sedation will be measured by observers using a 4-point sedation scale (0=fully awake, 1=mildly sedated (seldom drowsy and easy to awake), 2=moderately sedated (often drowsy and easy to awake), 3=severely sedated (somnolent, difficult to awake). Pruritis will also be measured using a 4-point scale (0=none, 3=severe). Any episodes of hypoventilation (respiratory rate < 8 breaths/min) or hypoxemia (oxygen saturation < 90%) during the study period will be recorded. Patient satisfaction with overall pain management will be determined using a 100-point verbal rating scale (1=highly dissatisfied (worst), 100=highly satisfied (best)). Respiratory rate, oxygen saturation (in ICU), and mean arterial blood pressure at the time of evaluation will be noted.
Postoperative pain will be managed according to standard institutional protocols. In the ICU, intravenous morphine will be administered for initial pain management (1 mg for mild-moderate pain, 2 mg for moderate-severe pain). Patients will be transitioned to oral pain medication when oral intake is tolerated (Norco tablets). The amount of pain medication administered during each study interval (listed above) will be recorded.
Other standard recovery variables will be recorded. These include time of initiation of ventilator weaning, time of tracheal extubation, arterial blood gas following extubation, time of ICU discharge, and time of hospital discharge. Time of first flatus and bowel movement will be recorded. Any complications during the hospitalization will be recorded. In a cohort of patients undergoing only coronary artery bypass graft surgery (n=75), serum troponins will be measured postoperatively to determine whether methadone has a potential cardioprotective effect.
Patients will be provided with a survey and self-addressed envelope following discharge from the hospital to determine the presence or absence of chronic persistent surgical pain. These data will be mailed by each patient 1, 3, 6, and 12 months postoperatively. The survey will assess the nature and severity of pain related to the surgical procedure.
- Conditions
- Pain, Postoperative, Chronic Pain
- Being tested
- Methadone, Fentanyl
- Keywords
- Fentanyl, Methadone, Thoracic Surgery
- Medical subject headings
- Pain, Postoperative, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Also called opioid
Methadone (0.3 mg/kg) will be administered intraoperatively, with half of the dose given at induction of anesthesia (over 5 minutes) and the remainder administered as an infusion over the next 2 hours.
FentanylDrug
Also called opioid
Fentanyl (12 mcg/kg) will be administered intraoperatively, with half of the dose given at induction of anesthesia (over 5 minutes) and the remainder administered as an infusion over the next 2 hours.
| Study group | Role | What they receive |
|---|---|---|
| Methadone | Experimental | Long-acting opioid Receives: Drug: Methadone |
| Fentanyl | Active comparator | Shorter-acting opioid Receives: Drug: Fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Opioid Consumption in the Postoperative Period
Total intravenous morphine used first three days (72 hours after ICU admission)
Measured: First 3 days after surgery
Secondary outcomes (6)
Postoperative Pain Scores
Pain was assessed on a 11-point verbal analogue scale with 0=no pain, 10=worst pain imaginable
Measured: 2 hours after cardiac surgery
Chronic Postoperative Pain Scores-Weekly Frequency of Pain
0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant
Measured: 1 months after surgery
Marker of Myocardial Injury (Troponin I)
In a cohort of patients undergoing only coronary artery bypass graft surgery (n=75), serum troponins will be measured postoperatively to determine whether methadone has a potential cardioprotective effect.
Measured: 12 hours after surgery
3 Months-Chronic Pain-weekly Frequency of Pain
0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant
Measured: 3 months
6 Months-Chronic Pain-weekly Frequency of Pain
0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant
Measured: 6 months
12 Months-Chronic Pain-weekly Frequency of Pain
0=< once per week; 1=once per week; 2=twice per week; 3=daily; 4=constant
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2012 (estimated)
- Study startSep 2010
- Primary completionNov 2013
- Study completionSep 2014
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 Pain, PostoperativeStudies 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
- 164 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
- NCT01542645
- Sponsor's protocol ID
- ENH10-256
- Status last verified
- Sep 2019
- First submitted
- 26 Feb 2012
- 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
- The Effect of Choice of Intraoperative Opioid on Postoperative Pain
- ClinicalTrials.gov ID
- NCT01542645
- Acronym / sponsor ID
- ENH10-256
- Conditions
- Pain, Postoperative, Chronic Pain
- Keywords
- Fentanyl, Methadone, Thoracic Surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 164 participants (actual)
- Lead sponsor
- Endeavor HealthUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Nov 2013 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 2 Mar 2012 (estimated)
- Results
- Posted 26 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary aim of this randomized, double-blind study is to examine the effect of a single intraoperative dose of methadone on postoperative pain and analgesic requirements in patients undergoing cardiac surgery with cardiopulmonary bypass. These patients will be compared to subjects receiving a standard dose of the "traditional" intraoperative opioid (fentanyl). Secondary outcome measures to be assessed will include standard recovery variables (such as length of postoperative intubation, ICU length of stay, incidence of nausea or vomiting, level of sedation). In addition, patients will be assessed for the development of chronic postoperative pain.
Detailed description
Patients will be randomized to receive either methadone or fentanyl on the basis of a computer generated random number table. Patients in each group will receive standard intraoperative doses of either methadone or fentanyl that will allow for early tracheal extubation (within 4-8 hours of the conclusion of the surgical procedure). Study infusions will be prepared by the pharmacy, and all clinicians will be blinded to group assignment (methadone group-0.3 mg/kg-100 mL normal saline; fentanyl group-12 μg/kg-100 mL normal saline).
Pain will be assessed by blinded observers using a 11-point verbal analogue scale (0=no pain, 10=worst pain imaginable). Assessment for pain will be performed 15 minutes post-extubation and then 2, 4, 8, 12, 24, 48, and 72 hours after tracheal extubation. Pain will be determined at rest, with coughing, and during movement. At the same time pain data is collected, several other clinical assessments will be completed. The presence or absence of nausea and vomiting will be determined, and severity quantified using a 4-point ordinal scale (0=none, 3=severe). Level of sedation will be measured by observers using a 4-point sedation scale (0=fully awake, 1=mildly sedated (seldom drowsy and easy to awake), 2=moderately sedated (often drowsy and easy to awake), 3=severely sedated (somnolent, difficult to awake). Pruritis will also be measured using a 4-point scale (0=none, 3=severe). Any episodes of hypoventilation (respiratory rate < 8 breaths/min) or hypoxemia (oxygen saturation < 90%) during the study period will be recorded. Patient satisfaction with overall pain management will be determined using a 100-point verbal rating scale (1=highly dissatisfied (worst), 100=highly satisfied (best)). Respiratory rate, oxygen saturation (in ICU), and mean arterial blood pressure at the time of evaluation will be noted.
Postoperative pain will be managed according to standard institutional protocols. In the ICU, intravenous morphine will be administered for initial pain management (1 mg for mild-moderate pain, 2 mg for moderate-severe pain). Patients will be transitioned to oral pain medication when oral intake is tolerated (Norco tablets). The amount of pain medication administered during each study interval (listed above) will be recorded.
Other standard recovery variables will be recorded. These include time of initiation of ventilator weaning, time of tracheal extubation, arterial blood gas following extubation, time of ICU discharge, and time of hospital discharge. Time of first flatus and bowel movement will be recorded. Any complications during the hospitalization will be recorded. In a cohort of patients undergoing only coronary artery bypass graft surgery (n=75), serum troponins will be measured postoperatively to determine whether methadone has a potential cardioprotective effect.
Patients will be provided with a survey and self-addressed envelope following discharge from the hospital to determine the presence or absence of chronic persistent surgical pain. These data will be mailed by each patient 1, 3, 6, and 12 months postoperatively. The survey will assess the nature and severity of pain related to the surgical procedure.
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 | Experimental | Drug: MethadoneLong-acting opioid |
| Fentanyl | Active comparator | Drug: FentanylShorter-acting opioid |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients presenting for elective cardiac surgery with CPB will be eligible for enrollment.
Key exclusion criteria (7 listed)
- Preoperative renal failure requiring dialysis
- Significant hepatic dysfunction (liver function tests > 2 times upper normal limit)
- Preoperative ejection fraction < 30%
- Pulmonary disease necessitating home oxygen therapy
- Preoperative requirement for inotropic agents or intraaortic balloon pump to maintain hemodynamic stability
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 |
|---|---|---|
| MethadoneAlso: opioidMethadone (0.3 mg/kg) will be administered intraoperatively, with half of the dose given at induction of anesthesia (over 5 minutes) and the remainder administered as an infusion over the next 2 hours. | Drug | Methadone |
| FentanylAlso: opioidFentanyl (12 mcg/kg) will be administered intraoperatively, with half of the dose given at induction of anesthesia (over 5 minutes) and the remainder administered as an infusion over the next 2 hours. | Drug | Fentanyl |
Primary outcome
Total Opioid Consumption in the Postoperative Period
Time frame: First 3 days after surgery
Total intravenous morphine used first three days (72 hours after ICU admission)
6 secondary outcomes
Postoperative Pain Scores
Time frame: 2 hours after cardiac surgery
Chronic Postoperative Pain Scores-Weekly Frequency of Pain
Time frame: 1 months after surgery
Marker of Myocardial Injury (Troponin I)
Time frame: 12 hours after surgery
3 Months-Chronic Pain-weekly Frequency of Pain
Time frame: 3 months
6 Months-Chronic Pain-weekly Frequency of Pain
Time frame: 6 months
12 Months-Chronic Pain-weekly Frequency of Pain
Time frame: 12 months
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 Fentanyl in people with Pain, Postoperative and Chronic 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 7 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 26 May 2014). 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 Opioid Consumption in the Postoperative Period (time frame: First 3 days after surgery). 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.