Spinal Hydromorphone Versus Morphine for Post-Cesarean Delivery Analgesia

March 31, 2023 updated by: Lawson Health Research Institute

Spinal Hydromorphone Versus Morphine for Post-Cesarean Delivery Analgesia: A Non-Inferiority Trial

Morphine is usually used for pain relief after cesarean delivery. However, sometimes it is not available, the patient might be allergic to morphine or intolerant to its side effects. Hydromorphone, another drug from the same class, might be used alternatively, but we need to prove that it is not inferior to morphine.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Spinal or intrathecal (IT) morphine is the most commonly used opioid for post-cesarean delivery analgesia. Factors that contribute to its widespread use include a favorable pharmacokinetic profile with duration of action up to 24 hours, ease of administration (during spinal block for surgical anesthesia) and low cost. Most providers administer 100 to 200 mcg of IT morphine for cesarean delivery analgesia with excellent analgesic results. Nevertheless, subarachnoid use of morphine is not without adverse events. While dose-dependent respiratory depression is the most worrisome complication, other side effects such as pruritus, nausea, vomiting and urinary retention can be bothersome during early puerperium. Furthermore, shortages of preservative free morphine in the United States has led clinicians to seek a reasonable alternative.

For the last 20 years, spinal hydromorphone has been successfully used for chronic pain associated with neoplasms. Its use for post-cesarean analgesia has been successfully reported. However, data regarding its efficacy in the IT space for post-cesarean analgesia is scarce. In the past, doses of 40 to 100 mcg have been reported to provide adequate postoperative pain relief with minimal side effects. In a recent study, the Effective Dose in 90% of patients has been established for both Hydromorphone and Morphine to be 75 mcg and 150 mcg, respectively.

No prospective studies have been conducted to specifically establish non-inferiority of hydromorphone when compared to morphine for post- cesarean analgesia. In addition, while all opioids share the same side effect profile, the frequency of those events are unknown for IT hydromorphone.

The current proposal is a blinded randomized controlled trial of intrathecal hydromorphone versus morphine in term pregnant women undergoing elective cesarean deliveries under spinal anesthesia.

Study Type

Interventional

Enrollment (Actual)

126

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • Victoria Hospital- LHSC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Age > 18 years; American Society of Anesthesiologist's Physical Status (ASA-PS) < 3; Term pregnancy (> 37 weeks gestational age); Elective cesarean delivery; Spinal Anesthesia;

Exclusion Criteria:

  • Documented allergy or severe intolerance to opioids; Intra-operative conversion to a general anesthetic technique; Chronic pain syndrome with baseline pain levels >3 on a visual analogue scale (0-10 cm); History of opioid use during this pregnancy; Allergy or intolerance to NSAIDS or acetaminophen; Morbid obesity- Body Mass Index (BMI) >40.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Spinal Hydromorphone
For the intervention group, 75 mcg of hydromorphone will be added to the spinal anesthetic mixture as a one-time injection prior to cesarean delivery.
Drug: Spinal Hydromorphone
75 mcg of hydromorphone will be prepared in a non-identifiable syringe by central hospital pharmacy. The resulting solution will then be added to the spinal anesthetic mixture(fentanyl 15 mcg and 0.75% hyperbaric bupivacaine 1.4-1.6 mcg at the discretion of the attending anesthesiologist, adjusted to height and weight)
Active Comparator: Spinal Morphine
For the control group,150 mcg of preservative-free morphine will be added to the spinal anesthetic mixture as a one-time injection prior to cesarean delivery.
Drug: Spinal Morphine
150 mcg of morphine will be prepared in a non-identifiable syringe by central hospital pharmacy.The resulting solution will be added to the spinal anesthetic mixture (fentanyl 15 mcg and 0.75% hyperbaric bupivacaine 1.4-1.6 mcg at the discretion of the attending anesthesiologist, adjusted to height and weight)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in the Average Numeric Rating Score (0-10 , where 0=no pain and 10= maximum pain) during the first 24 hours.
Time Frame: 24 hours after spinal anesthesia.
This is defined as the between- group difference in the average pain scores on a 0-10 Numeric Rating Scale, as assessed by a nurse, anesthesia consultant or trainee 24 hours after spinal anesthesia.
24 hours after spinal anesthesia.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in NRS pain scores at specific time points in the first 24 hours.
Time Frame: immediately after surgery (in PACU), 6, 12 and 18 hours after spinal anesthesia is given.
This is defined as the between- group difference in the mean pain scores on a 0-10 Numeric Rating Scale, as assessed by a nurse, anesthesia consultant or trainee immediately after surgery (in the Post-Anesthesia Care Unit) and at 6, 12, 18 and 24 hours after spinal anesthesia.
immediately after surgery (in PACU), 6, 12 and 18 hours after spinal anesthesia is given.
Time-to-first oral opioid analgesic request
Time Frame: Measured in hours from the time of spinal anesthetic until patient request for prescribed oral opioid analgesia, up to 24 hours from the spinal anesthetic .
This is defined as the length of time between spinal anesthesia and the first time the subject requested additional opioid analgesia, up to 24 hours from the spinal anesthesia.
Measured in hours from the time of spinal anesthetic until patient request for prescribed oral opioid analgesia, up to 24 hours from the spinal anesthetic .
Nausea and/or Vomiting that required treatment.
Time Frame: Absolute number of treatments required in the 24-hour time frame.
Nausea/Vomiting episodes that required pharmacological treatment in the first 24 hours after spinal anesthesia
Absolute number of treatments required in the 24-hour time frame.
Pruritus that required treatment.
Time Frame: Absolute number of treatments required in the 24-hour time frame.
Pruritus episodes that required pharmacological treatment in the first 24 hours after spinal anesthesia
Absolute number of treatments required in the 24-hour time frame.
Respiratory Depression
Time Frame: In post-anesthesia care unit (PACU), 6, 12, 18 and 24 hours after spinal anesthesia
Respiratory Rate measured in breaths/minute)
In post-anesthesia care unit (PACU), 6, 12, 18 and 24 hours after spinal anesthesia
Apgar Scores
Time Frame: 1 and 5 minutes after birth.
Neonatal Apgar scores at 1 and 5 minutes in a 1-10 interval scale
1 and 5 minutes after birth.
Difference in Opioid Consumption in the first 24 hours
Time Frame: 24 hours after spinal anesthesia.
This is defined as the between-group difference in the total amount of Oral Morphine Equivalents consumed in the first 24 hours after spinal anesthesia is given.
24 hours after spinal anesthesia.
Obstetric Quality of Recovery Score ObsQoR-11
Time Frame: 24 hours after spinal anesthesia.
11-item questionnaire applied to subjects 24 hours after spinal anesthesia. Measured in a 0-110 scale
24 hours after spinal anesthesia.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Investigators

  • Principal Investigator: Ilana Sebbag, MD, Western University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2020

Primary Completion (Actual)

July 28, 2022

Study Completion (Actual)

July 28, 2022

Study Registration Dates

First Submitted

March 26, 2018

First Submitted That Met QC Criteria

July 18, 2018

First Posted (Actual)

July 19, 2018

Study Record Updates

Last Update Posted (Actual)

April 3, 2023

Last Update Submitted That Met QC Criteria

March 31, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4357

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared after the end of this study other than publication of study results in medical journals.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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