Intrathecal Morphine for Cesarean Delivery

Optimal Dose of Intrathecal Morphine for Postoperative Analgesia After Cesarean Delivery

This is a randomized double blinded non-inferiority study comparing the duration of pain relief when patients receive one of three doses of spinal morphine. Enrolled patients will be randomly assigned to receive either 50 mcg, 150 mcg, or 250 mcg. All patients will receive standardized postoperative care, including multimodal analgesia. The primary outcome will be the time until the patient requests additional opioid pain medications.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Morphine Sulfate

Detailed Description

Prospective, randomized, double-blind, controlled trial, with a non-inferiority design. Patients will be randomly assigned to receive either intrathecal morphine 50 mcg, 150 mcg, or 250 mcg based on a pre-assigned randomization sequence. This medication will be administered as part of their spinal anesthesia for cesarean delivery. the patient, clinician who administers the spinal anesthesia, and investigator who follows the patient will all be blinded to the dose of medication.

All patients will receive standard of care for cesarean delivery and routine nursing care. This includes: preoperative intravenous catheter placement with preoperative IV fluid, standard American Society of Anesthesiologists monitoring, and neuraxial anesthesia placement (either spinal or combined spinal epidural) in sterile fashion. Each patient will receive standard cesarean induction dose of intrathecal medication consisting of 1.5ml of 0.75% hyperbaric bupivacaine, fentanyl 25 mcg. At end of surgery, all patients will receive standard dose of ketorolac 30 mg IV and acetaminophen 1 gm IV and continue with redosing every 6 and 8 hours (respectively) for 24 hours. On arrival to PACU, all patients will receive standard nursing care with standard monitoring of side effects. On discharge from PACU, patients will be transferred to postpartum floor and receive standard nursing care and monitoring.

Over the following 24 hours, the patient will receive all standard post-cesarean care. For treatment of breakthrough pain, medications will provided be per standard care: oxycodone 5-10 mg PO every four hours PRN for pain. If the patient is not comfortable after receiving oral oxycodone they will be assessed by an anesthesia provider for either regional nerve block or additional opioids, as a one-time dose or by patient controlled analgesia (PCA).

For treatment for side effects, medications will provided be per standard care: ondansetron 4mg IV as first-line for nausea/vomiting, promethazine 6.25 mg IV or Haloperidol 0.5-1mg IV for refractory nausea/vomiting. Naloxone 0.04 mg IV for refractory pruritus.

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Philip Hess; Phone Number: 6172832126; Email: phess@bidmc.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Philip E Hess, MD; Phone Number: 617-667-3112; Email: phess@bidmc.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy women (ASA 2)
• Between 18 and 45 years old
• Singleton term pregnancies
• Planned neuraxial anesthesia

Exclusion Criteria:

• Refusal to participate
• Known allergy or contraindication to any medication used in the study
• Significant medical or obstetrical disease (ASA ≥ 3)
• Opioid use disorder
• Chronic pain syndrome
• Daily or near daily opioid use within last 3 weeks.
• Patient receiving a Monoamine oxidase inhibitors (MOAi)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 50 micrograms; Patients in this arm will receive 50 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery	Drug: Morphine Sulfate; Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief
Active Comparator: 150 micrograms; Patients in this arm will receive 150 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery	Drug: Morphine Sulfate; Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief
Active Comparator: 250 micrograms; Patients in this arm will receive 250 micrograms of morphine administered in the spinal fluid as part of their anesthesia for cesarean delivery	Drug: Morphine Sulfate; Morphine is administered to provide pain relief after cesarean delivery; this is an assessment of the dose-response as measured by the duration of pain relief

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of pain relief	Time to patient request for first dose of oral rescue pain medicine	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores	Visual analogue pain scores reported by the patient. Scale measured on a line from 0 to 100 mm, with 0 representing 'no pain' and 100 representing 'worst possible pain'	24 hours
Quality of recovery	Quality of Recovery Score following Cesarean Delivery Questionnaire (ObsQoR-11). This is a multi-dimensional wellness scale ranging from 0 (worst) to 10 (best) along 12 axis items.	24 hours
Nausea	Incidence of nausea and vomiting requiring treatment with a medication	24 hours
Pruritus	Incidence of pruritus requiring treatment with a medication	24 hours

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: September 25, 2021
• First Submitted That Met QC Criteria: September 25, 2021
• First Posted (Actual): October 6, 2021

Study Record Updates

• Last Update Posted (Actual): January 21, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: morphine; cesarean; multimodal analgesia
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: 2021P000688

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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.: No