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Intrathecal Opioids for Pain Control After Cesarean Delivery: Determining the Optimal Dose

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hans P. Sviggum, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02009722
First received: December 9, 2013
Last updated: June 23, 2016
Last verified: June 2016
  Purpose
Both hydromorphone and morphine are administered as part of spinal anesthesia to help improve pain control after cesarean delivery. In this study, the investigators are going to determine the doses of each of those medicines that provides optimal pain control to women undergoing cesarean delivery while limiting side effects related to those medicines. The investigators hypothesize that the doses of hydromorphone and morphine that provide optimal pain control without significant side effects will be 100 micrograms and 150 micrograms, respectively. The investigators further hypothesize that at each respective optimal dose, side effects will be less in the hydromorphone group.

Condition Intervention Phase
Analgesia, Obstetrical
Cesarean Section
Drug: Morphine
Drug: Hydromorphone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intrathecal Opioids for Pain Control After Cesarean Delivery: Determining the Optimal Dose

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Dose of IT Morphine and IT Hydromorphone for Adequate Analgesia (Pain Score Less Than or Equal to 3) in 90% of Patients [ Time Frame: 12 hours after administration of spinal anesthesia ] [ Designated as safety issue: No ]
    Each patient will be interviewed by a member of the study team 12 hours after receiving their spinal anesthetic (which will include either hydromorphone or morphine). Patients will be asked to rate their current level of pain on a scale of 0 (no pain) to 10 (worst pain imaginable). A pain score <4 will be considered a success. The up-down sequential allocation method will be used to determine the dose (mcg) of IT hydromorphone and IT morphine for subsequent patients


Secondary Outcome Measures:
  • Side Effects: Pruritus [ Time Frame: 6 hours after spinal administration ] [ Designated as safety issue: No ]
    Patients will be evaluated by a member of the study team at 6 hours after spinal administration. The number of patients with moderate or severe pruritus will be recorded.

  • Side Effects: Nausea [ Time Frame: 6 hours after spinal ] [ Designated as safety issue: No ]
    Patients will be evaluated by a member of the study team at 6 hours after spinal administration. Patients with moderate or severe nausea will be recorded.

  • Side Effects: Sedation [ Time Frame: 6, 12, and 24 hours after spinal administration ] [ Designated as safety issue: Yes ]
    Patients will be evaluated by a member of the study team at 6, 12, and 24 hours after spinal administration. The presence of sedation will be graded by the Richmond Agitation Sedation Scale. Patients with a score of (-)2 or lower on the Richmond were classified as being positive for sedation.

  • Pruritus [ Time Frame: 12 hours after spinal ] [ Designated as safety issue: No ]
    Patients will be evaluated by a member of the study team at 12 hours after spinal administration. The number of patients with moderate or severe pruritus will be recorded.

  • Pruritus [ Time Frame: 24 hours after spinal ] [ Designated as safety issue: No ]
    Patients will be evaluated by a member of the study team at 24 hours after spinal administration. The number of patients with moderate or severe pruritus will be recorded.

  • Nausea [ Time Frame: 12 hours after spinal ] [ Designated as safety issue: No ]
    Patients will be evaluated by a member of the study team at 12 hours after spinal administration. The number of patients with moderate or severe nausea will be recorded.

  • Nausea [ Time Frame: 24 hours after spinal ] [ Designated as safety issue: No ]
    Patients will be evaluated by a member of the study team at 24 hours after spinal administration. The number of patients with moderate or severe nausea will be recorded.

  • Treatment for Nausea [ Time Frame: First 24 hours ] [ Designated as safety issue: No ]
    number of patients needing medication treatment for nausea in first 24 hours

  • Treatment for Pruritus [ Time Frame: First 24 hours after spinal ] [ Designated as safety issue: No ]
    The number of patients needing medical treatment for pruritus in first 24 hours after surgery


Enrollment: 84
Study Start Date: January 2014
Study Completion Date: April 2015
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intrathecal hydromorphone
Patients will be randomized to receive a one-time dose of intrathecal hydromorphone or intrathecal morphine as part of their spinal anesthesia. The starting dose of intrathecal hydromorphone will be 40 micrograms. This will be adjusted in subsequent patients based on the previous patient's success or failure according to an up-and-down methodology utilizing a biased coin design.
Drug: Hydromorphone
Hydromorphone (Dilaudid) is administered in the intrathecal space for post-operative pain control
Other Name: Dilaudid
Active Comparator: Intrathecal morphine
Patients will be randomized to receive a one-time dose of intrathecal hydromorphone or intrathecal morphine as part of their spinal anesthesia. The starting dose of intrathecal morphine will be 100 micrograms. This will be adjusted in subsequent patients based on the previous patient's success or failure according to an up-and-down methodology utilizing a biased coin design.
Drug: Morphine
Duramorph is administered as part of spinal anesthesia for post-operative pain relief.
Other Name: Duramorph

Detailed Description:

Spinal anesthesia is the most common anesthetic technique used for Cesarean delivery in the United States and across the world. Intrathecal opioids are administered along with a local anesthetic during spinal anesthesia for Cesarean delivery to provide postoperative analgesia. The effectiveness of intrathecal morphine for post-Cesarean pain control is well established, but the effectiveness of intrathecal hydromorphone in this patient population is limited to case reports and small retrospective studies. No prospective studies have been conducted to establish the effectiveness of intrathecal hydromorphone for post-Cesarean pain.

Hydromorphone has been studied extensively as a substitute for intrathecal morphine in patients with chronic noncancer pain. In fact, a recent consensus article placed hydromorphone as a first line therapy along with morphine for intrathecal pain management. Its ability to treat post-Cesarean pain when administered in the epidural space has been known for quite some time, but its effects in the intrathecal space are less established. In patients undergoing Cesarean delivery, intrathecal doses of 40 to 100 micrograms have been reported to provide good pain scores postoperatively with only minimal side effects. Doses of up to 300 micrograms have been used, leading to excellent pain control without out respiratory depression, but with significant pruritus and nausea.

Although reducing pain, intrathecal opioids are associated with side effects including pruritus, nausea, and respiratory depression. 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 have found that hydromorphone causes less nausea and pruritus than morphine, while others have not. Although opioid-induced respiratory depression is a rare event, studies evaluating intrathecal hydromorphone for post-Cesarean delivery pain have not reported any cases of respiratory depression.

The optimal dose of intrathecal morphine for analgesia following Cesarean delivery is still debated and the efficacy of intrathecal hydromorphone has not been studied extensively in this patient population. The investigators aim to identify the dose of each medication that provides good pain relief without causing significant side effects. The investigators will then perform a comparative analysis of each drug at their optimal dose.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women presenting for elective cesarean delivery with no major co-morbidities, including pregnancy induced co-morbidities (e.g. pre-eclampsia)
  • Singleton gestation at term (37-42 weeks)
  • Desire to have a spinal anesthesia technique for cesarean delivery

Exclusion Criteria:

  • Current or historical evidence of clinically significant medical disease or condition
  • Any contraindication to the administration of a spinal technique for anesthesia
  • History of hypersensitivity or idiosyncratic reaction to opioid medications
  • Chronic pain syndrome or current regular opioid use
  • Evidence of anticipated fetal anomalies
  • Allergy or intolerance to Tylenol, ketorolac, ibuprofen, or oxycodone
  • BMI > 40
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02009722

Locations
United States, Minnesota
Rochester Methodist Hospital, Mayo Clinic
Rochester, Minnesota, United States, 55902
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Hans P Sviggum, M.D. Mayo Clinic
  More Information

Publications:

Responsible Party: Hans P. Sviggum, M.D., Assistant Professor of Anesthesiology, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02009722     History of Changes
Other Study ID Numbers: 13-008490 
Study First Received: December 9, 2013
Results First Received: March 15, 2016
Last Updated: June 23, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Cesarean Delivery
Intrathecal Morphine
Intrathecal Hydromorphone
Obstetrical Analgesia
Spinal Anesthesia

Additional relevant MeSH terms:
Anesthetics
Morphine
Hydromorphone
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Opioid
Narcotics
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2016