Dexamethasone for Post Traumatic Headache

NCT04799015 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 2020-12625UL1TR001073
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized study of intravenous metoclopramide + intravenous dexamethasone versus intravenous metoclopramide for patients with acute post-traumatic headache.

Conditions

Post-Traumatic Headache

Outcome Measures

Primary Outcomes (1)

• Frequency of Moderate or Severe Headache After Emergency Department (ED) Discharge

  Headache intensity will be rated based on the International Headache Society (IHS) 4-point scale. Using this scale participants will verbalize whether their headache intensity is "Severe," "Moderate," "Mild," or "None." The percentage of patients reporting a headache intensity level of either "Moderate" or "Severe" will be grouped and summarized by study arm. The number/percentage of patients reporting a headache intensity level of "Mild" or "None" will also be grouped and summarized by study arm. Between-group difference along with 95% confidence intervals will be reported. Patients who use an analgesic or abortive headache medication during the 48-hour period will be considered an outcome failure.

  From ED discharge to 48-hours following discharge from the ED, up to 2 days total

Secondary Outcomes (4)

• Sustained Headache Relief

  48 hours after administration of study medication

• Post Concussive Symptoms

  48 hours after ED discharge, up to 2 days total

• Post Concussive Symptoms

  7 days after ED discharge, up to 7 days total

• Use of Rescue Medication in the ED

  Duration of ED admission, less than 1 day

Other Outcomes (1)

• Number of Days With Headache During the Week After ED Discharge

  Up to 1 week after ED discharge, up to 7 days total

Study Arms (2)

Dexamethasone

EXPERIMENTAL

Dexamethasone 10mg IV + metoclopramide 10mg IV

Drug: Dexamethasone; Drug: Metoclopramide 10mg

Placebo

PLACEBO COMPARATOR

Placebo IV + metoclopramide 10mg IV

Drug: Metoclopramide 10mg

Interventions

Dexamethasone DRUG

Dexamethasone 10mg IV

Dexamethasone

Metoclopramide 10mg DRUG

Metoclopramide 10mg IV

Dexamethasone; Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet International Classification of Headache Disorders (3rd edition) criteria for acute post-traumatic headache as follows:
• Traumatic injury to the head has occurred
• Headache has developed within 7 days of injury to the head
• Headache is not better accounted for by another diagnosis (e.g., migraine or tension-type headache)
• The headache must be rated as moderate or severe in intensity at the time of initial evaluation

You may not qualify if:

• More than ten days have elapsed since the head trauma
• Headache has already been treated with an anti-dopaminergic medication
• Medication allergies
• Contra-indications including pheochromocytoma, seizure disorder, Parkinson's disease, use of Monoamine oxidase (MAO) inhibitors, and use of anti-rejection transplant medications

Sponsors & Collaborators

• Montefiore Medical Center: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Montefiore

The Bronx, New York, 10467, United States

Location

Related Publications (20)

• Blyth BJ, Bazarian JJ. Traumatic alterations in consciousness: traumatic brain injury. Emerg Med Clin North Am. 2010 Aug;28(3):571-94. doi: 10.1016/j.emc.2010.03.003.

  PMID: 20709244 BACKGROUND

• Evans RW. The Postconcussion Syndrome and Posttraumatic Headaches in Civilians, Soldiers, and Athletes. Neurol Clin. 2024 May;42(2):341-373. doi: 10.1016/j.ncl.2023.12.001. Epub 2024 Jan 16.

  PMID: 38575256 BACKGROUND

• Shah R, Das S, Gentile Kruse CF, de Prado BM, Raj N, Evans M, Panigrahi P, Hershey AD, Master CL, Szperka CL, Patterson Gentile C. Patterns of Use and Benefit of Triptans in the Treatment of Acute Headache Worsening in Youth With Post-Traumatic Headache. Pediatr Neurol. 2025 Jun;167:96-102. doi: 10.1016/j.pediatrneurol.2025.03.013. Epub 2025 Mar 27.

  PMID: 40252247 BACKGROUND

• Patterson Gentile C, Shah R, Irwin SL, Greene K, Szperka CL. Acute and chronic management of posttraumatic headache in children: A systematic review. Headache. 2021 Nov;61(10):1475-1492. doi: 10.1111/head.14236. Epub 2021 Dec 4.

  PMID: 34862612 BACKGROUND

• Larsen EL, Ashina H, Iljazi A, Al-Khazali HM, Seem K, Ashina M, Ashina S, Schytz HW. Acute and preventive pharmacological treatment of post-traumatic headache: a systematic review. J Headache Pain. 2019 Oct 21;20(1):98. doi: 10.1186/s10194-019-1051-7.

  PMID: 31638888 BACKGROUND

• Friedman BW, Irizarry E, Cain D, Caradonna A, Minen MT, Solorzano C, Zias E, Zybert D, McGregor M, Bijur PE, Gallagher EJ. Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache. Neurology. 2021 May 4;96(18):e2323-e2331. doi: 10.1212/WNL.0000000000011822. Epub 2021 Mar 24.

  PMID: 33762421 BACKGROUND

• Orr SL, Friedman BW, Christie S, Minen MT, Bamford C, Kelley NE, Tepper D. Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2016 Jun;56(6):911-40. doi: 10.1111/head.12835.

  PMID: 27300483 BACKGROUND

• Bramley H, Melinosky C, Silvis M, Ross S. Pediatric posttraumatic headache: two cases using steroids as abortive therapy. Pediatr Emerg Care. 2012 Oct;28(10):1081-4. doi: 10.1097/PEC.0b013e31826ceeeb.

  PMID: 23034499 BACKGROUND

• Navratilova E, Rau J, Oyarzo J, Tien J, Mackenzie K, Stratton J, Remeniuk B, Schwedt T, Anderson T, Dodick D, Porreca F. CGRP-dependent and independent mechanisms of acute and persistent post-traumatic headache following mild traumatic brain injury in mice. Cephalalgia. 2019 Dec;39(14):1762-1775. doi: 10.1177/0333102419877662. Epub 2019 Sep 24.

  PMID: 31550910 BACKGROUND

• Kamins J. Models for Treating Post-traumatic Headache. Curr Pain Headache Rep. 2021 Jun 14;25(8):52. doi: 10.1007/s11916-021-00970-3.

  PMID: 34125320 BACKGROUND

• Zeng Z, Wei L, Zhang H, Chen W, Wang S. The Effect of Dexamethasone on Neuroinflammation and Cerebral Edema in Rats With Traumatic Brain Injury Combined With Seawater Drowning. Cureus. 2024 Mar 1;16(3):e55309. doi: 10.7759/cureus.55309. eCollection 2024 Mar.

  PMID: 38559532 BACKGROUND

• Barlow KM. Post-traumatic headache: An unmet medical need. Headache. 2021 Nov;61(10):1465-1466. doi: 10.1111/head.14241. No abstract available.

  PMID: 34928511 BACKGROUND

• May A, Evers S, Goadsby PJ, Leone M, Manzoni GC, Pascual J, Carvalho V, Romoli M, Aleksovska K, Pozo-Rosich P, Jensen RH; European Academy of Neurology Task Force. European Academy of Neurology guidelines on the treatment of cluster headache. Eur J Neurol. 2023 Oct;30(10):2955-2979. doi: 10.1111/ene.15956. Epub 2023 Jul 28.

  PMID: 37515405 BACKGROUND

• Headache 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.

  PMID: 29368949 BACKGROUND

• Latev A, Friedman BW, Irizarry E, Solorzano C, Restivo A, Chertoff A, Zias E, Gallagher EJ. A Randomized Trial of a Long-Acting Depot Corticosteroid Versus Dexamethasone to Prevent Headache Recurrence Among Patients With Acute Migraine Who Are Discharged From an Emergency Department. Ann Emerg Med. 2019 Feb;73(2):141-149. doi: 10.1016/j.annemergmed.2018.09.028. Epub 2018 Nov 16.

  PMID: 30449536 BACKGROUND

• Friedman BW, Solorzano C, Kessler BD, Martorello K, Lutz CL, Feliciano C, Adler N, Moss H, Cain D, Irizarry E. Randomized Trial Comparing Low- vs High-Dose IV Dexamethasone for Patients With Moderate to Severe Migraine. Neurology. 2023 Oct 3;101(14):e1448-e1454. doi: 10.1212/WNL.0000000000207648. Epub 2023 Aug 21.

  PMID: 37604662 BACKGROUND

• Ashina H, Diener HC, Tassorelli C, Scher AI, Lipton RB, Pozo-Rosich P, Sinclair AJ, Chong CD, Finkel AG, Ashina M, Schwedt TJ, Dodick DW, Terwindt GM. Guidelines of the International Headache Society for controlled trials of pharmacological preventive treatment for persistent post-traumatic headache attributed to mild traumatic brain injury. Cephalalgia. 2024 Mar;44(3):3331024241234068. doi: 10.1177/03331024241234068.

  PMID: 38518177 BACKGROUND

• Diener HC, Tassorelli C, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ, Mandrekar J; International Headache Society Clinical Trials Standing Committee. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia. 2019 May;39(6):687-710. doi: 10.1177/0333102419828967. Epub 2019 Feb 26.

  PMID: 30806518 BACKGROUND

• Chin EY, Nelson LD, Barr WB, McCrory P, McCrea MA. Reliability and Validity of the Sport Concussion Assessment Tool-3 (SCAT3) in High School and Collegiate Athletes. Am J Sports Med. 2016 Sep;44(9):2276-85. doi: 10.1177/0363546516648141. Epub 2016 Jun 8.

  PMID: 27281276 BACKGROUND

• Friedman BW, Babbush K, Irizarry E, White D, John Gallagher E. An exploratory study of IV metoclopramide+diphenhydramine for acute post-traumatic headache. Am J Emerg Med. 2018 Feb;36(2):285-289. doi: 10.1016/j.ajem.2017.10.034. Epub 2017 Oct 13.

  PMID: 29074068 BACKGROUND

MeSH Terms

Conditions

Post-Traumatic Headache

Interventions

Dexamethasone; Metoclopramide

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Results Point of Contact

• Title: Dr. Benjamin Friedman
• Organization: Montefiore Medical Center

befriedm@montefiore.org

718-920-6626

Study Officials

• Benjamin Friedman, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization occurred in a 1:1 ratio in blocks of four.

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 16, 2021
• Study Start: June 25, 2021
• Primary Completion: November 17, 2024
• Study Completion: December 22, 2024
• Last Updated: May 15, 2026
• Results First Posted: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Upon approval of the analytic plan.

Locations

US (1)