2 Dose Neuraxial Morphine for Prevention of PDPH

January 14, 2025 updated by: Richard M. Smiley, Columbia University

Two Dose Neuraxial Morphine for Prevention of Postdural Puncture Headache

Neuraxial analgesia (most commonly continuous epidural or combined spinal epidural) is the most effective modality available for pain relief during labor. Accidental dural puncture (ADP) with a large bore epidural needle and the resulting post-dural puncture headache (PDPH) is one of the most significant sources of anesthesia-related morbidity in parturients.

Epidural blood patch (EBP) is the gold standard for treatment of PDPH, and although almost always effective, can result in another ADP, as well as low back pain and lower extremity pain. For this reason, effective measures to prevent PDPH when ADP occurs would be highly valuable. One small study in which 50 women were randomly allocated to receive 2 epidural injections of morphine or saline, demonstrated a beneficial effect of epidural morphine in decreasing the incidence of PDPH.

This study aims to determine the efficacy of 2 doses of neuraxial (either epidural (EPID) or intrathecal) preservative-free morphine (PFM) to prevent headache after ADP in parturients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This will be a prospective, randomized, double blind clinical trial. Subjects will be ASA I and II women (per American Society of Anesthesiologists Physical Status Classification System or ASA) aged 18 years and older, who are known to have had ADP with an epidural needle during placement of neuraxial labor analgesia, and have either an intrathecal catheter or epidural catheter in situ. Patients will be randomized to either receive PFM or placebo (sterile normal saline (NS or SAL)).

For patients with an epidural catheter, the group "EPID PFM" will receive 3 mg (6 ml) of PFM, followed by 3 ml of sterile normal saline to be administered through the epidural catheter. The placebo group, "EPID NS", will receive 6 ml of sterile normal saline via the epidural catheter followed by another 3 ml NS. For patients with an intrathecal catheter, the group, "IT PFM" will receive 200 micrograms (mcg) (0.4 ml) of preservative-free morphine, followed by a flush of the catheter with 2 ml of sterile saline. The placebo group will receive 0.4 ml and then 2 ml of sterile normal saline through the intrathecal catheter. Sixteen to 24 hours after receiving the first study drug, patients in all groups will be visited by an investigator, and then daily thereafter during the hospital admission. They will be evaluated for the presence of headache, analgesia requirements, need for EBP and the severity of opioid side effects. As long as the patient is afebrile, has not been experiencing severe opioid side effects and the catheter is in place and intact, the patient will then receive the identical study drug (for a total of two doses). The epidural/intrathecal catheter will be removed immediately after the second administration of the study drug.

After discharge, the patient will be followed up once daily by telephone for up to a minimum of 5 days after receiving the last dose of the study drug if they remain headache free, and for a minimum of 3 days after resolution of PDPH.

Statistical Design:

This will be a prospective randomized double blind clinical trial. The primary outcome will be the incidence of PDPH at 48 hours after ADP. The primary outcome of the trial is the incidence of PDPH at 48 hours after ADP. We will consider a difference in incidence of PDPH between the placebo and treatment groups of 25 % to be significant, based on the findings of Al Metwalli et al. (Anaesthesia. 2008; 63(8):847-50), and the meta-analysis by Heesen et al. (Int J Obstet Anesth. 2013 ; 22(1):26-30).

Estimates of PDPH rate after ADP range from 50 to 85%. Our rate at Columbia University Irving Medical Center (CUIMC) for the past several years is 66% (OB Anesthesia Division QA data). For calculation of our sample size, we determined that an absolute 25% decrease in PDPH would be clinically significant (i.e., 66% to ~40%). For a power of 90% and an alpha of 0.05, this requires 83 subjects per group (2 epidural groups compared to each other, 2 spinal groups compared to each other). We are not specifically powering this for comparison of the spinal to the epidural groups, although we will likely be able to do so. We therefore, aim to recruit 100 subjects per group (for a total of 400 across all centers) assuming 10-15% of subjects may be lost because of inadvertent withdrawal of the catheter, subject withdrawal, or lost to follow up after discharge.

This is intended to be a multicenter study involving 5 academic tertiary hospitals, having >2,000 vaginal deliveries per year. Since the rate of accidental dural puncture is between 1 and 2%, we estimate we should be able to recruit 100 subjects per year. Categorical data (presence or absence of dural puncture headache, need for epidural blood patch) will be analyzed using Chi-square analysis.

Study Type

Interventional

Enrollment (Actual)

44

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

  • United States
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Rutgers Health University Hospital
    • New York
      • New York, New York, United States, 10032
        • New York Presbyterian Hospital
      • New York, New York, United States, 10021
        • Weill Cornell Medical Center
      • New York, New York, United States, 10467
        • Montefiore Hospital

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

Yes

Description

Inclusion Criteria:

  • Subjects will be ASA I and II women aged 18 years and older, who are known to have had accidental dural puncture with an epidural needle during placement of neuraxial labor analgesia, and have either an intrathecal catheter or epidural catheter in place.

Exclusion Criteria:

  • Past history of headache syndromes- such as migraine and cluster headaches
  • History of chronic pain syndromes
  • Chronic opioid use
  • Illicit drug use - e.g. marijuana, heroin
  • Allergy to morphine
  • Intrapartum or postpartum fever ≥ 38 ° C
  • Coagulopathy
  • Accidental removal of the epidural or intrathecal catheter

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: EPID PFM
The group "EPID PFM" will receive 3 mg (6 ml) of preservative-free morphine, followed by 3 ml of sterile normal saline, to be administered through the epidural catheter.Sixteen to 24 hours after receiving the first study drug, the patient will then receive the identical study drug (for a total of two doses).
Drug: Morphine
preservative free morphine given either via an epidural or intrathecal catheter
Other Names:
  • Duramorph
Drug: Sterile normal saline
sterile normal saline, given either via an epidural or intrathecal catheter
Other Names:
  • Saline
Sham Comparator: EPID SAL
The placebo group, "EPID NS", will receive 6 ml of sterile normal saline via the epidural catheter followed by another 3 ml NS. Sixteen to 24 hours after receiving the first study drug,the patient will then receive the identical study drug (for a total of two doses).
Drug: Sterile normal saline
sterile normal saline, given either via an epidural or intrathecal catheter
Other Names:
  • Saline
Active Comparator: IT PFM
The group, "IT PFM" will receive 200 micrograms (mcg) (0.4 ml) of preservative-free morphine via the intrathecal catheter, followed by a flush of the catheter with 2 ml of sterile saline.Sixteen to 24 hours after receiving the first study drug, the patient will then receive the identical study drug (for a total of two doses).
Drug: Morphine
preservative free morphine given either via an epidural or intrathecal catheter
Other Names:
  • Duramorph
Drug: Sterile normal saline
sterile normal saline, given either via an epidural or intrathecal catheter
Other Names:
  • Saline
Sham Comparator: IT SAL
The placebo group IT SAL will receive 0.4 ml and then 2 ml of sterile normal saline through the intrathecal catheter.Sixteen to 24 hours after receiving the first study drug, the patient will then receive the identical study drug (for a total of two doses).
Drug: Sterile normal saline
sterile normal saline, given either via an epidural or intrathecal catheter
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Postdural Puncture Headache
Time Frame: 48 hours after accidental dural puncture
The primary outcome will be the incidence of postdural puncture headache at 48 hours after accidental dural puncture. This will be determined by a face to face questionnaire and the severity of headache will be rated according to a verbal rating scale (0 -10).
48 hours after accidental dural puncture

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants in Need for Epidural Blood Patch
Time Frame: 48 hours after accidental dural puncture
A secondary outcome will be the need for epidural blood patch at 48 hours after accidental dural puncture. This will be recorded on the study data collection sheet.
48 hours after accidental dural puncture

Collaborators and Investigators

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

Sponsor

Columbia University

Collaborators

Montefiore Medical Center
Weill Medical College of Cornell University
Rutgers University

Investigators

  • Principal Investigator: Richard Smiley, MD, PhD, Columbia 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

September 1, 2015

Primary Completion (Actual)

January 1, 2020

Study Completion (Actual)

January 1, 2020

Study Registration Dates

First Submitted

June 3, 2015

First Submitted That Met QC Criteria

June 12, 2015

First Posted (Estimated)

June 16, 2015

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 14, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAP4755

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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