Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04752033 |
| Other study ID # |
20-009205 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
March 10, 2021 |
| Est. completion date |
February 17, 2023 |
Study information
| Verified date |
March 2024 |
| Source |
Mayo Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This research study is being done to determine the optimal dose of spinal morphine and
hydromorphone in patients undergoing minimally-invasive (i.e., surgery performed through
small entry sites and using cameras) colorectal surgery.
Description:
Intrathecal (IT) opioids have been established as a safe and efficacious modality to treat
postoperative pain. In the setting of colorectal surgery, studies have shown that intrathecal
opioids together with multimodal analgesic regimens provide pain relief superior to
multimodal analgesia alone. Furthermore, in the setting of multimodal analgesia, IT opioids
also appear to be equianalgesic to epidural analgesia while conferring an improved safety
profile. As a result, many institutions have incorporated intrathecal opioids into their
Enhanced Recovery after Surgery (ERAS) pathways.
While morphine has traditionally been considered the "gold standard" in IT opioid therapy for
postsurgical pain, hydromorphone has been gaining popularity as an alternative. The doses
ranging between 0.005 mg to 0.25 mg for hydromorphone12-15 and 0.05 mg to 0.625 mg (with
doses as high as 10 mcg/kg in the setting of cardiac surgery) for morphine has been found to
be efficacious in this patient population. However, increasing opioid doses are associated
with increased incidence of adverse effects. A meta-analysis reviewing twenty-eight studies
which investigated intrathecal morphine versus placebo demonstrated moderate increases in the
incidences of pruritus, nausea and vomiting. In fact, the incidence of nausea with IT
morphine has been reported to be 33%. While hydromorphone is similar chemically to morphine,
it is metabolized differently. Differences in pharmacokinetics may allow for differences in
side effect profiles. Hydromorphone is more lipid soluble than morphine. This decreases its
spread within the intrathecal space and enhances its penetration into the dorsal horn of the
spinal cord where interactions with opioid receptors occur. Some studies (performed in the
women undergoing cesarean delivery) have also found that hydromorphone causes less nausea and
pruritus than morphine, while others have not.
Despite the widespread use of IT hydromorphone and morphine for pain after colorectal
surgery, the optimal dose for neither drug has been established in prospective trials. The
investigators have previously performed a dose-finding study of IT hydromorphone and morphine
in women undergoing cesarean delivery. Briefly, 80 parturients scheduled for elective
cesarean delivery were randomized to receive IT morphine or IT hydromorphone at a dose
determined using up-down sequential allocation with a biased-coin design to determine ED90,
which was found to be 75 mcg for IT hydromorphone and 150 mcg for IT morphine. The follow-up
study performed by the investigators also found no differences in adverse effects or efficacy
between the drugs. The results from the obstetric population, however, cannot be directly
translated to the colorectal surgery population due to pharmacodynamic and pharmacokinetics
differences related to the pregnancy, age, presence of comorbidities, differences in surgical
techniques, and co-administration of IT local anesthetic.
This study applies the methodology the investigators have previously used in the obstetric
population to the patients undergoing colorectal resection and aims to identify the optimal
dose of IT hydromorphone and morphine that provides good pain relief without causing
significant side effects. Secondarily, the investigators will compare each drug at its
optimal dose in terms of opioid consumption and side effects. Based on their prior findings,
the investigators hypothesize that the optimal dose of intrathecal hydromorphone will be 75
mcg and the optimal dose of intrathecal morphine will be 150 mcg. Additionally, the
investigators hypothesize that exploratory findings comparing the two drugs at their optimal
doses will show no difference in the incidence of adverse effects.
