Cosyntropin Versus Epidural Blood Patch (EBP) for Treatment of Treatment of Post Dural Puncture Headache
Condition: Postdural Puncture Headache
MeSH terms: Post-Dural Puncture Headache; Headache; Wounds and Injuries
Study type: Interventional
Phase: Phase 4

Summary: 
      PDPH is a common problem after either intentional or unintentional Dural puncture. It is
      especially common in young female patients and in patients undergoing Lumbar Puncture using
      the typical kit containing large 20 gauge needles (1).

      Hypothesis is that Cosyntropin therapy is at least as effective as current conservative
      therapy (caffeine/fluid) and/or Epidural Blood Patch.

      Patients will be randomly assigned to undergo either: (1) EBP with IVF therapy or
      (2)Cosyntropin IV with IVF therapy. Endpoints will be a pain score that is given prior to the
      procedure, Emergency Department (ED) discharge pain score and post procedural day (PPD) day
      1, day 3 and day 7 pain and functional levels. Patients in Cosyntropin arm of the study may
      request crossover to EBP at anytime after a 24 hour assessment period is completed per
      Standard of Care for treatment of PDPH, in order to ensure no undue distress is placed on the
      patient in order to complete this study.

      Current treatments consist primarily of non-invasive treatment with intravenous fluids and
      caffeine therapy and invasive treatment by Epidural Blood Patch. Efficacy of Caffeine 300mg
      IV bis in die (BID) x 1d doses is approximately 70% (2). However this therapy has been linked
      to post-treatment seizures. EBP was originally thought to be 90% effective with repeat
      treatment efficacy approaching >96%. However more recent studies by Taivainen et al (3) have
      shown only a 61% rate of permanent cure. Additionally, EBP are contraindicated in patients
      with signs of increased intra-cranial pressure (ICP), coagulation issues, signs/symptoms of
      Central Nervous System (CNS) /systemic infection or local infection at the site of the EBP,
      thus resulting in decreased utility. Complications are also quite serious ranging from
      meningitis, spinal hematoma, repeat dural puncture, localized infection and vagal response to
      the procedure. EBP are not typically performed until after conservative measures have failed
      which leads to further prolongation of the patients decreased functional status and pain.
      Additionally, the cost of both treatments is substantial considering prolonged ED visits for
      conservative treatments often followed by the time and expense of an EBP.

      The goal of this investigation is to aid in the confirmation of case reports advocating the
      economy, efficacy and safety of synthetic Adrenal CorticTropin Hormone (ACTH) as a treatment
      of PDPH (4,5,6,7,8,9).
    

Detailed description: 
      PDPH is a common problem after either intentional or unintentional Dural puncture. It is
      especially common in young female patients and in patients undergoing Lumbar Puncture using
      the typical kit containing large 20 gauge needles (1).

      Current treatments consist primarily of non-invasive treatment with intravenous fluids and
      caffeine therapy and invasive treatment by Epidural Blood Patch. Efficacy of Caffeine 300mg
      IV BID x 1d doses is approximately 70% (2). However this therapy has been linked to
      post-treatment seizures. EBP was originally thought to be 90% effective with repeat treatment
      efficacy approaching >96%. However more recent studies by Taivainen et al (3) have shown only
      a 61% rate of permanent cure. Additionally, EBP are contraindicated in patients with signs of
      increased ICP, coagulation issues, signs/symptoms of CNS/systemic infection or local
      infection at the site of the EBP, thus resulting in decreased utility. Complications are also
      quite serious ranging from meningitis, spinal hematoma, repeat dural puncture, localized
      infection and vagal response to the procedure. EBP are not typically performed until after
      conservative measures have failed which leads to further prolongation of the patients
      decreased functional status and pain. Additionally, the cost of both treatments is
      substantial considering prolonged ED visits for conservative treatments often followed by the
      time and expense of an EBP.

      The goal of this investigation is to aid in the confirmation of case reports advocating the
      economy, efficacy and safety of synthetic ACTH as a treatment of PDPH (4,5,6,7,8,9).

      After patients receive and sign an informed consent form (ICF) Patients will be randomly
      assigned to undergo either: (1) EBP with IVF therapy or (2)Cosyntropin IV with IVF therapy.
      Endpoints will be a pain score that is given prior to the procedure, ED discharge pain score
      and post procedural day (PPD) day 1, day 3 and day 7 pain and functional levels. Patients in
      Cosyntropin arm of the study may request crossover to EBP at anytime after a 24 hour
      assessment period is completed per Standard of Care for treatment of PDPH, in order to ensure
      no undue distress is placed on the patient in order to complete this study.

      Investigational New Drug (IND) Exemption for use of Cosyntropin.

      Research Objective: To develop an efficacious and cost effective alternative to Epidural
      Blood Patch and Caffeine therapy for Postdural Puncture Headache.

      Two Study Groups: (1) Group A - Cosyntropin 500 mcg in 1000 mili-liters Normal Saline (NS)
      run over 1 hour (2) Group B - Epidural Blood Patch and 1000 mili-liters NS

        -  1liter NS run over 1 hour while waiting for call team to place Epidural Blood Patch

        -  Std Epidural Kit using 18g tuohy needle to Loss of Resistance (LOR) with providers
           preferred medium

        -  Max 20 cc of sterile blood in epidural space with amount dictated by either 20cc or sig
           pain/pressure

        -  Pt supine for 30 minutes post procedure

      Randomization Procedures: Computer generated random number list with even numbers receiving
      Cosyntropin and odd numbers receiving traditional epidural blood patch.

      Methods and Materials: After referral to an Anesthesiologist and confirmation of PDPH
      diagnosis, patient will be randomized to either Cosyntropin or Epidural Blood Patch assuring
      they are negative for pregnancy. If enrolled in Cosyntropin arm a bag of premixed (by
      pharmacy) Cosyntropin 500mcg in a 1 liter Normal Saline bag of Intravenous Fluid will be run
      over 1 hour. Please see above for further details. Additionally, there will be a telephone
      follow-up questionnaire performed by a person not directly involved with the study to collect
      data as described above.

      Standard of Care: Patients are evaluated by the ED, clinic, labor deck or pre-op area and if
      PDPH is suspected patient is offered and given conservative treatment with intravenous
      caffeine. If this treatment fails and/or the patient requests it, the Anesthesia team is
      notified for possible EBP.

      Experimental Procedure: Randomly selected patients will receive Cosyntropin 500mcg IV in 1
      liter NS vs EBP

      Research Material Collected: Verbal Analogue Scale scores and improvement in functional
      status. Pt's will be identified by a Patient ID number which will not be the same as the
      patient's hospital Identification (ID) or Social Security Number (SSN). Contact information
      will be kept on a separate patient tracking sheet (see attached) and kept electronically on a
      password protected computer.

      Subject Recruiting: All patients meeting inclusion requirements will be offered enrollment at
      time of diagnosis/treatment.

      Justification of Subject Population: Patient's with PDPH often have significant pain levels
      and subsequent decreases in function. Recent literature notes decreased efficacy of invasive
      Epidural Blood Patches. Alternate, less invasive techniques, could decrease time to relief
      and allow treatment patients with contra-indications to Epidural Blood Patch.

      Risks: Local Infection, meningitis, allergic reaction, spinal hematoma, nerve damage,
      paralysis, failure of procedure, new dural puncture. Incidence of adverse events will be
      tracked.

        1. Justification of Risks- Control arm is current standard of care for this patient
           population. Experimental group utilizes a medication that has a very low risk profile.
           This medication is often used in the ICU setting on the most critical ill without
           increased risk.

        2. Minimization of Risks- Control arm is current standard of care. Experimental group will
           be treated in monitored settings of either the Emergency Department, Post- Anesthesia
           Care Unit (PACU) or L&D PACU

        3. Medical Monitor- A medical Monitor will be appointed

      Benefits: Optimization of pain control for patients with PDPH. Will provide an alternative
      method to treat those patients with PDPH who have contra-indications to EBP. Will
      significantly reduce cost/personnel for treatment of PDPH and give options to medical
      providers in remote regions of care without the training/equipment to perform EBP.

      Statistical Analysis: Data analysis will be accomplished using descriptive and inferential
      statistics. Demographic data will be analyzed using Student's t-test. Frequency data will be
      compared with the Chi-square test. A student's t-test will be used to compare the verbal pain
      scores. The satisfaction scores will be compared with a Mann-Whitney U test. A p-value of <
      0.05 will be considered significant. All analysis will be performed utilizing
      Intention-to-Treat analysis and clearly state in the results section the number of persons
      that switch from the cosyntropin group to epidural blood patch therapy. The efficacy of the
      EBP for the study group and for this "crossover" group will also be noted.
    

Intervention name(s): Cosyntropin; Epidural Blood Patch
Intervention type(s): Drug; Procedure
Intervention description(s): Intravenous Drug Infusion over 1 hour and a half; Blood drawn from subject and then same Blood placed into Epidural space by anesthesia personnel.
Other intervention name(s): Tetracosactin; Blood patch
Intervention MeSH terms: Cosyntropin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Postdural puncture headache; Epidural Blood Patch; Cosyntropin; PDPH; Regional anesthesia; Lumbar puncture; ACTH; Tetracosactin