Spinal Hydromorphone Versus Morphine for Post-Cesarean Delivery Analgesia

NCT03592992 | Completed Phase 4 FDA Drug

• 1 other identifier: 4357
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Pain

Outcome Measures

Primary Outcomes (1)

• Difference in the Average Numeric Rating Score (0-10 , where 0=no pain and 10= maximum pain) during the first 24 hours.

  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 Outcomes (8)

• Difference in NRS pain scores at specific time points in the first 24 hours.

  immediately after surgery (in PACU), 6, 12 and 18 hours after spinal anesthesia is given.

• Time-to-first oral opioid analgesic request

  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.

  Absolute number of treatments required in the 24-hour time frame.

• Pruritus that required treatment.

  Absolute number of treatments required in the 24-hour time frame.

• Respiratory Depression

  In post-anesthesia care unit (PACU), 6, 12, 18 and 24 hours after spinal anesthesia

Study Arms (2)

Spinal Hydromorphone

EXPERIMENTAL

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

Spinal Morphine

ACTIVE COMPARATOR

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

Interventions

Spinal Hydromorphone DRUG

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)

Spinal Hydromorphone

Spinal Morphine DRUG

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)

Spinal Morphine

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female subjects that are term pregnant at the time of recruitment.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

Victoria Hospital- LHSC

London, Ontario, N6A 5A5, Canada

Location

Related Publications (16)

• Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship of intrathecal morphine for postcesarean analgesia. Anesthesiology. 1999 Feb;90(2):437-44. doi: 10.1097/00000542-199902000-00018.

  PMID: 9952150 BACKGROUND

• Rathmell JP, Pino CA, Taylor R, Patrin T, Viani BA. Intrathecal morphine for postoperative analgesia: a randomized, controlled, dose-ranging study after hip and knee arthroplasty. Anesth Analg. 2003 Nov;97(5):1452-1457. doi: 10.1213/01.ANE.0000083374.44039.9E.

  PMID: 14570664 BACKGROUND

• Wong JY, Carvalho B, Riley ET. Intrathecal morphine 100 and 200 mug for post-cesarean delivery analgesia: a trade-off between analgesic efficacy and side effects. Int J Obstet Anesth. 2013 Jan;22(1):36-41. doi: 10.1016/j.ijoa.2012.09.006. Epub 2012 Nov 15.

  PMID: 23159009 BACKGROUND

• Milner AR, Bogod DG, Harwood RJ. Intrathecal administration of morphine for elective Caesarean section. A comparison between 0.1 mg and 0.2 mg. Anaesthesia. 1996 Sep;51(9):871-3. doi: 10.1111/j.1365-2044.1996.tb12622.x.

  PMID: 8882255 BACKGROUND

• Girgin NK, Gurbet A, Turker G, Aksu H, Gulhan N. Intrathecal morphine in anesthesia for cesarean delivery: dose-response relationship for combinations of low-dose intrathecal morphine and spinal bupivacaine. J Clin Anesth. 2008 May;20(3):180-5. doi: 10.1016/j.jclinane.2007.07.010.

  PMID: 18502360 BACKGROUND

• Gerancher JC, Floyd H, Eisenach J. Determination of an effective dose of intrathecal morphine for pain relief after cesarean delivery. Anesth Analg. 1999 Feb;88(2):346-51. doi: 10.1097/00000539-199902000-00023.

  PMID: 9972754 BACKGROUND

• Ventola CL. The drug shortage crisis in the United States: causes, impact, and management strategies. P T. 2011 Nov;36(11):740-57. No abstract available.

  PMID: 22346307 BACKGROUND

• Deer TR, Smith HS, Burton AW, Pope JE, Doleys DM, Levy RM, Staats PS, Wallace MS, Webster LR, Rauck RL, Cousins M; Center For Pain Relief, Inc. Comprehensive consensus based guidelines on intrathecal drug delivery systems in the treatment of pain caused by cancer pain. Pain Physician. 2011 May-Jun;14(3):E283-312.

  PMID: 21587338 BACKGROUND

• Dougherty TB, Baysinger CL, Henenberger JC, Gooding DJ. Epidural hydromorphone with and without epinephrine for post-operative analgesia after cesarean delivery. Anesth Analg. 1989 Mar;68(3):318-22.

  PMID: 2465709 BACKGROUND

• Parker RK, Sawaki Y, White PF. Epidural patient-controlled analgesia: influence of bupivacaine and hydromorphone basal infusion on pain control after cesarean delivery. Anesth Analg. 1992 Nov;75(5):740-6. doi: 10.1213/00000539-199211000-00015.

  PMID: 1384397 BACKGROUND

• Beatty NC, Arendt KW, Niesen AD, Wittwer ED, Jacob AK. Analgesia after Cesarean delivery: a retrospective comparison of intrathecal hydromorphone and morphine. J Clin Anesth. 2013 Aug;25(5):379-383. doi: 10.1016/j.jclinane.2013.01.014. Epub 2013 Aug 17.

  PMID: 23965210 BACKGROUND

• Rauch E. Intrathecal hydromorphone for postoperative analgesia after cesarean delivery: a retrospective study. AANA J. 2012 Aug;80(4 Suppl):S25-32.

  PMID: 23248827 BACKGROUND

• Sviggum HP, Arendt KW, Jacob AK, Niesen AD, Johnson RL, Schroeder DR, Tien M, Mantilla CB. Intrathecal Hydromorphone and Morphine for Postcesarean Delivery Analgesia: Determination of the ED90 Using a Sequential Allocation Biased-Coin Method. Anesth Analg. 2016 Sep;123(3):690-7. doi: 10.1213/ANE.0000000000001229.

  PMID: 26974022 BACKGROUND

• Rauch E. Intrathecal hydromorphone for cesarean delivery: in search of improved postoperative pain management: a case report. AANA J. 2011 Oct;79(5):427-32.

  PMID: 23256273 BACKGROUND

• Ciechanowicz S, Setty T, Robson E, Sathasivam C, Chazapis M, Dick J, Carvalho B, Sultan P. Development and evaluation of an obstetric quality-of-recovery score (ObsQoR-11) after elective Caesarean delivery. Br J Anaesth. 2019 Jan;122(1):69-78. doi: 10.1016/j.bja.2018.06.011. Epub 2018 Jul 31.

  PMID: 30579408 BACKGROUND

• Cheng S, Bartolacci J, Armstrong K, Dobrowlanski A, Jones PM, Singh SI, Sebbag I. Intrathecal Hydromorphone Versus Intrathecal Morphine for Postcesarean Delivery Analgesia: A Randomized Noninferiority Trial. Anesth Analg. 2026 Jan 1;142(1):19-27. doi: 10.1213/ANE.0000000000007580. Epub 2025 Jun 10.

  PMID: 40493496 DERIVED

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Ilana Sebbag, MD

  Western University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Allocation concealment will be achieved through central pharmacy randomization with the use of a master randomization list of computer-generated random numbers prior to initiation of recruitment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Institutional Research Ethics Board Approval was obtained (Western Research Ethics Board 111264). Term pregnant women presenting to the Obstetric Care Unit at Victoria Hospital for an elective cesarean delivery will be approached for recruitment. Consenting participants will be randomly assigned to receive either 75 mcg of hydromorphone or 150 mcg of morphine at the time of their spinal anesthetic. Randomization will be achieved through a simple computerized randomization technique (use of random numbers list for allocation).

Study Record Dates

• First Submitted: March 26, 2018
• First Posted: July 19, 2018
• Study Start: November 11, 2020
• Primary Completion: July 28, 2022
• Study Completion: July 28, 2022
• Last Updated: April 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)