Post-Dural Puncture HeadachePhase 4NCT05289323
Effect of Intrathecal Neostigmine on Post-dural Puncture Headache.
A Phase 4 study testing Neostigmine Methylsulfate and Dextrose 5%/Nacl 0.9% Inj in people with Post-Dural Puncture Headache, run by Alexandria University at 1 site in Egypt.
Trial summary
Intravenous neostigmine was recently reported as an effective treatment for PDPH for parturients after intrathecal (IT) block which is postulated to be through its central effects on CSF secretion and cerebral vascular tone modulation. Read more about this study
- Who is it for?
- Ages 20 to 40 years, women only
- Conditions the study is for
- Post-Dural Puncture Headache
- What is being tested?
- Neostigmine Methylsulfate and Dextrose 5%/Nacl 0.9% Inj
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 722 participants
- Where
- 1 siteEgypt
- Study dates
- 25 Apr 2022to 25 Jul 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- American society association (ASA) physical status class II parturients with a single fetus who will be scheduled for an elective caesarian section by Intrathecal block.
Who cannot join
- Body mass index more than or equal to 35 kg/m2.
- Any contraindication to Intrathecal blocks such as local infection, bleeding disorders, or parturient refusal.
- Allergy to neostigmine or other drugs will be used in the study.
- Long-term opioid use.
- A history of chronic pain, migraine, cluster headache.
- Digestive problems with nausea and vomiting; cognitive dysfunction or memory disorders.
Show all 10Show fewer
- Significant renal, hepatic, and cardiovascular diseases.
- History of urinary retention or bronchial asthma.
- Inadequate or failed Intrathecal block.
- Complicated pregnancy such as hypertensive disorders of the pregnancy, abnormal placenta, or uterine atony.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Intrathecal Neostigmine as an Adjuvant to Bupivacaine in Ameliorating Post-Dural Puncture Headache in Elective Caesarian Section: A Prospective Randomized Controlled Clinical Trial
Intravenous neostigmine was recently reported as an effective treatment for PDPH for parturients after intrathecal (IT) block which is postulated to be through its central effects on CSF secretion and cerebral vascular tone modulation. Intrathecal neostigmine has been investigated widely and found to be an effective adjuvant to bupivacaine for postoperative analgesia.
The objective of the current study is to investigate the possible prophylactic role of intrathecal neostigmine as an adjuvant to bupivacaine in reducing the incidence and severity of post-dural puncture headache in parturients scheduled for an elective cesarean section.
Read the detailed description
Upon arrival to the operating room standard monitors will be applied and continued all over the operation, an 18G peripheral intravenous (IV) cannula will be inserted, and 15 ml/kg of Ringer lactate solution will be infused.
The intrathecal block will be performed via a midline approach into the L3-4 or L4-5 interspaces in a sitting position under strict aseptic condition using a 25-gauge spinal needle after administration of 3 ml of lidocaine 2% (60 mg) as a subcutaneous infiltration, a 2.5 ml of hyperbaric bupivacaine, 0.5 % (12.5 mg) in addition to the content of the prepared study syringe will be mixed and slowly injected.
After ensuring sufficient anesthesia level by loss of sensation to pinprick at the T4 level, the surgical procedure will start with continuous hemodynamic monitoring and recording.
At the end of the surgery, the parturient will be transferred to the postoperative anesthesia care unit (PACU).
Parturients will be transferred to the obstetrics ward after fulfilling the criteria of the modified Aldrete scoring system ≥9.
The participants who will be diagnosed to have PDPH Per the previously mentioned criteria will be treated by using oral Panadol extra™ (paracetamol 1gm + caffeine 135 mg) (Manufactured by: Alexandria company for pharmaceuticals \& chemical industries under license: GlaxoSmithKline Consumer Healthcare Ltd. Ireland) at 6-hour interval in addition to ensuring good oral or intravenous hydration (2-3 L/day) and bed rest. Severe Intractable headache (VAS ≥ 4) persistent for more than 48 hours with no response to conservative measures will be managed with an autologous epidural blood patch after participant approval and consent signing.
Assessment of the quality of the sensory and motor block in terms of the onset and duration will be done at 2 minutes intervals during the first 10 minutes after giving the spinal block, then at 10 minutes intervals until the end of the surgery, and at 15 minutes intervals while being in the PACU.
- Conditions
- Post-Dural Puncture Headache
- Being tested
- Neostigmine Methylsulfate, Dextrose 5%/Nacl 0.9% Inj
- Keywords
- Neostigmine, Intrathecal, prevention of PDPH, PDPH, Caesarean section
- Medical subject headings
- Post-Dural Puncture Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neostigmine MethylsulfateDrug
Also called Neostigmine 20 mic
0.5 mg ampule (1 ml) will be diluted in 4 ml dextrose 5% to make a solution of 100 μg/ml, 0.2 ml of this solution will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection.
Dextrose 5%/Nacl 0.9% InjDrug
Also called Dextrose 5 %Nacl0.9%
one ml of normal saline 0.9 % will be mixed with 4 ml dextrose 5 % in the five-milliliter syringe. 0.2 ml of this mixture will be prepared at a one-milliliter identical syringe.
| Study group | Role | What they receive |
|---|---|---|
| The Intervention group (N) | Experimental | 0.5 mg ampule (1 ml) will be diluted in 4 ml dextrose 5% to make a solution of 100 μg/ml, 0.2 ml of this solution will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection. Receives: Drug: Neostigmine Methylsulfate |
| The control group (C) | Placebo comparator | one ml of normal saline 0.9 % will be mixed with 4 ml dextrose 5 % in the five-milliliter syringe. 0.2 ml of this mixture will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection. Receives: Drug: Dextrose 5%/Nacl 0.9% Inj |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of post-dural puncture headache
any headache that develops within five days of dural puncture and can't be attributed to any other types of headache and mostly is postural in character.usually associated with neck stiffness, nausea, photophobia, and subjective hearing symptoms
Measured: Two times daily for five days after intrathecal block.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2022
- Study start25 Apr 2022
- Primary completion25 Jul 2023
- Study completion25 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Post-Dural Puncture HeadacheStudies of the same condition, open and under way.
- More trials run by Alexandria UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 722 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexandria University
- Sponsor type
- University, hospital or other
- Collaborators
- Kasr El Aini Hospital, Fayoum University
- Responsible party
- Principal investigator, Ahmed Ismail Elnaggar, Alexandria University
- Investigators
- Hisham M Gamal Eldine, MD, Study director, University of AlexandriaAhmed I Elnaggar, MD, Principal investigator, University of Alexandria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05289323
- Sponsor's protocol ID
- IRB NO: 00012098 SN: 0305408
- Status last verified
- Jul 2023
- First submitted
- 13 Mar 2022
- Last updated
- 27 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Turnbull DK, Shepherd DB. Post-dural puncture headache: pathogenesis, prevention and treatment. Br J Anaesth. 2003 Nov;91(5):718-29. doi: 10.1093/bja/aeg231.
PubMed 14570796Arevalo-Rodriguez I, Ciapponi A, Munoz L, Roque i Figuls M, Bonfill Cosp X. Posture and fluids for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2013 Jul 12;(7):CD009199. doi: 10.1002/14651858.CD009199.pub2.
PubMed 23846960Grant R, Condon B, Hart I, Teasdale GM. Changes in intracranial CSF volume after lumbar puncture and their relationship to post-LP headache. J Neurol Neurosurg Psychiatry. 1991 May;54(5):440-2. doi: 10.1136/jnnp.54.5.440.
PubMed 1865208Abdelaal Ahmed Mahmoud A, Mansour AZ, Yassin HM, Hussein HA, Kamal AM, Elayashy M, Elemady MF, Elkady HW, Mahmoud HE, Cusack B, Hosny H, Abdelhaq M. Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache: A Randomized Controlled Trial. Anesth Analg. 2018 Dec;127(6):1434-1439. doi: 10.1213/ANE.0000000000003734.
PubMed 30169405Prabhakar A, Lambert T, Kaye RJ, Gaignard SM, Ragusa J, Wheat S, Moll V, Cornett EM, Urman RD, Kaye AD. Adjuvants in clinical regional anesthesia practice: A comprehensive review. Best Pract Res Clin Anaesthesiol. 2019 Dec;33(4):415-423. doi: 10.1016/j.bpa.2019.06.001. Epub 2019 Jul 2.
PubMed 31791560Aldrete JA. Modifications to the postanesthesia score for use in ambulatory surgery. J Perianesth Nurs. 1998 Jun;13(3):148-55. doi: 10.1016/s1089-9472(98)80044-0.
PubMed 9801540Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.
PubMed 29368949Cesarini M, Torrielli R, Lahaye F, Mene JM, Cabiro C. Sprotte needle for intrathecal anaesthesia for caesarean section: incidence of postdural puncture headache. Anaesthesia. 1990 Aug;45(8):656-8. doi: 10.1111/j.1365-2044.1990.tb14392.x.
PubMed 2400077Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009 Nov;41(4):1149-60. doi: 10.3758/BRM.41.4.1149.
PubMed 19897823
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Intrathecal Neostigmine as an Adjuvant to Bupivacaine in Ameliorating Post-Dural Puncture Headache in Elective Caesarian Section: A Prospective Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT05289323
- Acronym / sponsor ID
- IRB NO: 00012098 SN: 0305408
- Conditions
- Post-Dural Puncture Headache
- Keywords
- Neostigmine, Intrathecal, prevention of PDPH, PDPH, Caesarean section
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 722 participants (actual)
- Lead sponsor
- Alexandria UniversityUniversity, hospital or other
- Collaborators
- Kasr El Aini Hospital, Fayoum University
- Study start
- 25 Apr 2022 (actual)
- Primary completion
- 25 Jul 2023 (actual)
- Study completion
- 25 Jul 2023 (actual)
- First posted
- 21 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Intravenous neostigmine was recently reported as an effective treatment for PDPH for parturients after intrathecal (IT) block which is postulated to be through its central effects on CSF secretion and cerebral vascular tone modulation. Intrathecal neostigmine has been investigated widely and found to be an effective adjuvant to bupivacaine for postoperative analgesia.
The objective of the current study is to investigate the possible prophylactic role of intrathecal neostigmine as an adjuvant to bupivacaine in reducing the incidence and severity of post-dural puncture headache in parturients scheduled for an elective cesarean section.
Detailed description
Upon arrival to the operating room standard monitors will be applied and continued all over the operation, an 18G peripheral intravenous (IV) cannula will be inserted, and 15 ml/kg of Ringer lactate solution will be infused.
The intrathecal block will be performed via a midline approach into the L3-4 or L4-5 interspaces in a sitting position under strict aseptic condition using a 25-gauge spinal needle after administration of 3 ml of lidocaine 2% (60 mg) as a subcutaneous infiltration, a 2.5 ml of hyperbaric bupivacaine, 0.5 % (12.5 mg) in addition to the content of the prepared study syringe will be mixed and slowly injected.
After ensuring sufficient anesthesia level by loss of sensation to pinprick at the T4 level, the surgical procedure will start with continuous hemodynamic monitoring and recording.
At the end of the surgery, the parturient will be transferred to the postoperative anesthesia care unit (PACU).
Parturients will be transferred to the obstetrics ward after fulfilling the criteria of the modified Aldrete scoring system ≥9.
The participants who will be diagnosed to have PDPH Per the previously mentioned criteria will be treated by using oral Panadol extra™ (paracetamol 1gm + caffeine 135 mg) (Manufactured by: Alexandria company for pharmaceuticals \& chemical industries under license: GlaxoSmithKline Consumer Healthcare Ltd. Ireland) at 6-hour interval in addition to ensuring good oral or intravenous hydration (2-3 L/day) and bed rest. Severe Intractable headache (VAS ≥ 4) persistent for more than 48 hours with no response to conservative measures will be managed with an autologous epidural blood patch after participant approval and consent signing.
Assessment of the quality of the sensory and motor block in terms of the onset and duration will be done at 2 minutes intervals during the first 10 minutes after giving the spinal block, then at 10 minutes intervals until the end of the surgery, and at 15 minutes intervals while being in the PACU.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| The Intervention group (N) | Experimental | Drug: Neostigmine Methylsulfate0.5 mg ampule (1 ml) will be diluted in 4 ml dextrose 5% to make a solution of 100 μg/ml, 0.2 ml of this solution will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection. |
| The control group (C) | Placebo comparator | Drug: Dextrose 5%/Nacl 0.9% Injone ml of normal saline 0.9 % will be mixed with 4 ml dextrose 5 % in the five-milliliter syringe. 0.2 ml of this mixture will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- American society association (ASA) physical status class II parturients with a single fetus who will be scheduled for an elective caesarian section by Intrathecal block.
Key exclusion criteria (10 listed)
- Body mass index more than or equal to 35 kg/m2.
- Any contraindication to Intrathecal blocks such as local infection, bleeding disorders, or parturient refusal.
- Allergy to neostigmine or other drugs will be used in the study.
- Long-term opioid use.
- A history of chronic pain, migraine, cluster headache.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neostigmine MethylsulfateAlso: Neostigmine 20 mic0.5 mg ampule (1 ml) will be diluted in 4 ml dextrose 5% to make a solution of 100 μg/ml, 0.2 ml of this solution will be added to 2.5 ml of hyperbaric bupivacaine 0.5 % used for intrathecal injection. | Drug | The Intervention group (N) |
| Dextrose 5%/Nacl 0.9% InjAlso: Dextrose 5 %Nacl0.9%one ml of normal saline 0.9 % will be mixed with 4 ml dextrose 5 % in the five-milliliter syringe. 0.2 ml of this mixture will be prepared at a one-milliliter identical syringe. | Drug | The control group (C) |
Primary outcome
Incidence of post-dural puncture headache
Time frame: Two times daily for five days after intrathecal block.
any headache that develops within five days of dural puncture and can't be attributed to any other types of headache and mostly is postural in character.usually associated with neck stiffness, nausea, photophobia, and subjective hearing symptoms
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
- Results publication: PubMed 14570796Turnbull DK, Shepherd DB. Post-dural puncture headache: pathogenesis, prevention and treatment. Br J Anaesth. 2003 Nov;91(5):718-29. doi: 10.1093/bja/aeg231.
- Results publication: PubMed 23846960Arevalo-Rodriguez I, Ciapponi A, Munoz L, Roque i Figuls M, Bonfill Cosp X. Posture and fluids for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2013 Jul 12;(7):CD009199. doi: 10.1002/14651858.CD009199.pub2.
- Results publication: PubMed 1865208Grant R, Condon B, Hart I, Teasdale GM. Changes in intracranial CSF volume after lumbar puncture and their relationship to post-LP headache. J Neurol Neurosurg Psychiatry. 1991 May;54(5):440-2. doi: 10.1136/jnnp.54.5.440.
- Results publication: PubMed 30169405Abdelaal Ahmed Mahmoud A, Mansour AZ, Yassin HM, Hussein HA, Kamal AM, Elayashy M, Elemady MF, Elkady HW, Mahmoud HE, Cusack B, Hosny H, Abdelhaq M. Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache: A Randomized Controlled Trial. Anesth Analg. 2018 Dec;127(6):1434-1439. doi: 10.1213/ANE.0000000000003734.
- Results publication: PubMed 31791560Prabhakar A, Lambert T, Kaye RJ, Gaignard SM, Ragusa J, Wheat S, Moll V, Cornett EM, Urman RD, Kaye AD. Adjuvants in clinical regional anesthesia practice: A comprehensive review. Best Pract Res Clin Anaesthesiol. 2019 Dec;33(4):415-423. doi: 10.1016/j.bpa.2019.06.001. Epub 2019 Jul 2.
- Results publication: PubMed 9801540Aldrete JA. Modifications to the postanesthesia score for use in ambulatory surgery. J Perianesth Nurs. 1998 Jun;13(3):148-55. doi: 10.1016/s1089-9472(98)80044-0.
- Results publication: PubMed 29368949Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.
- Results publication: PubMed 2400077Cesarini M, Torrielli R, Lahaye F, Mene JM, Cabiro C. Sprotte needle for intrathecal anaesthesia for caesarean section: incidence of postdural puncture headache. Anaesthesia. 1990 Aug;45(8):656-8. doi: 10.1111/j.1365-2044.1990.tb14392.x.
- Results publication: PubMed 19897823Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009 Nov;41(4):1149-60. doi: 10.3758/BRM.41.4.1149.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hisham M Gamal Eldine, MD study director
University of Alexandria
Ahmed I Elnaggar, MD principal investigator
University of Alexandria
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Neostigmine Methylsulfate and Dextrose 5%/Nacl 0.9% Inj in people with Post-Dural Puncture Headache, run by Alexandria University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of post-dural puncture headache (time frame: Two times daily for five days after intrathecal block.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05289323, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.