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2 Dose Neuraxial Morphine for Prevention of PDPH

This study is currently recruiting participants.
Verified July 2017 by Richard M. Smiley, Columbia University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02473276
First Posted: June 16, 2015
Last Update Posted: July 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Richard M. Smiley, Columbia University
  Purpose

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.


Condition Intervention Phase
Postdural Puncture Headache Drug: Morphine Drug: Sterile normal saline Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Two Dose Neuraxial Morphine for Prevention of Postdural Puncture Headache

Resource links provided by NLM:


Further study details as provided by Richard M. Smiley, Columbia University:

Primary Outcome Measures:
  • Percent 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).


Secondary Outcome Measures:
  • Percent 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.


Estimated Enrollment: 400
Study Start Date: September 2015
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Duramorph
Drug: Sterile normal saline
sterile normal saline, given either via an epidural or intrathecal catheter
Other Name: 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 Name: 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 Name: Duramorph
Drug: Sterile normal saline
sterile normal saline, given either via an epidural or intrathecal catheter
Other Name: 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 Name: Saline

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 CUMC 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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02473276


Contacts
Contact: Richard Smiley, MD, PhD rms7@cumc.columbia.edu
Contact: Allison Lee, MD al3196@cumc.columbia.edu

Locations
United States, New Jersey
Rutgers-Newark Recruiting
Newark, New Jersey, United States, 07103
Principal Investigator: Dongchen Li, MD         
United States, New York
New York Presbyterian Hospital Recruiting
New York, New York, United States, 10032
Contact: Allison Lee, MD       al3196@columbia.edu   
Contact: Richard Smiley, MD, PhD       rms7@cumc.columbia.edu   
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Richard Smiley, MD, PhD Columbia University
  More Information

Publications:
Responsible Party: Richard M. Smiley, Virginia Apgar M.D. Professor of Anesthesiology, Chief of Obstetric Anesthesia, Columbia University
ClinicalTrials.gov Identifier: NCT02473276     History of Changes
Other Study ID Numbers: AAAP4755
First Submitted: June 3, 2015
First Posted: June 16, 2015
Last Update Posted: July 25, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Headache
Post-Dural Puncture Headache
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Headache Disorders, Secondary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents