MAD: A Cost Effective Treatment for Headache in Pregnancy When Acetaminophen Alone is Ineffective.

• Sponsor: St. Louis University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02295280
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

To determine if the intravenous administration of Metoclopramide and diphenhydramine in combination can effectively treat headaches in pregnant patients in those refractory to acetaminophen when compared to codeine

Condition or Disease	Intervention/Treatment	Phase
Headache	Drug: Metoclopramide; Drug: Diphenhydramine; Drug: Codeine	N/A

Detailed Description

This is a randomized, controlled study based on prospective collection of data during the study subjects' hospital stays, questioning at 30 minutes and 1, 6, and 24 hours after administration, and a post-study questionnaire at 24 hours. Subjects who agree to participate in the study will have already tried a standard effective dose of acetaminophen (650 to 1000mg) without relief and are requesting further medication. Intravenous (IV) access will be obtained and administration of 10mg Metoclopramide IV and 25mg Diphenhydramine IV drawn up in the same syringe will be given to subjects randomized to Group A, while those randomized to Group B (control group) will receive standard treatment consisting of a codeine 30mg tablet. Each subject will be asked if they had relief or persistence/recurrence of symptoms at 30 minutes, 1 hour and 6 hours after initial receipt of study medications. An additional dose of 10 mg IV metoclopramide + 25 mg IV diphenhydramine or codeine 30 mg tablets would be given at one hour if the patient did not have adequate relief the first time. If headache does not subside or recurs after second dose, regular non protocol medicines may be administered upon doctor recommendation. Patients will again be asked about headache at 24 hours and asked to complete a questionnaire regarding tolerance of medication, any adverse reactions experienced, persistence/recurrence of headache after administration of study medication, timing of occurrence with regard to administration, requirements of a second dose of study medication or other use of headache or nausea medication not included in protocol, satisfaction or relief of headache on a Likert scale from 0 to 10 after administration of medication if given at 1 hr interval.

Randomization Subjects will be randomized to GROUP A or GROUP B. An order will be placed to the SMHC pharmacy for the respective Group and will send up the medication assigned. The pharmacy will know which medications are in Group A and which are in Group B. On the pharmacy order sheet, the research team will indicate which group each subject is randomized to. The pharmacy will supply the medications and one of the nurses on the 5th floor will administer them.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Metoclopramide and Diphenhydramine (MAD): A Cost Effective Treatment for Headache in Pregnancy When Acetaminophen Alone is Ineffective (MAD Headache Study)
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metoclopramide IV & Diphenhydramine IV Intravenous (IV) access will be obtained and administration of 10mg Metoclopramide IV and 25mg Diphenhydramine IV Group A	Drug: Metoclopramide; IV; Other Names: metoclopramide, Reglan, Reglan ODT, Metozol ODT, Octamide, ; Drug: Diphenhydramine; iv; Other Names: Benadryl
Active Comparator: Codeine Group B (control group) will receive standard treatment consisting of a codeine 30mg tablet.	Drug: Codeine; PO

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adequate Relief of Headache as a Measure of Efficacy [Primary outcome was six hours post administration]

   Number of participants with reduction in pain scores six hours post administration by at least 2 on the pain score scale.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Pregnant women age 16 or older, admitted to the hospital or treated in the triage unit at 14 weeks gestation or greater, with subjective symptoms of persistent headache despite 650-1000 mg acetaminophen taken more than one hour before administration of study medication.

Exclusion Criteria:

Treatment with another headache-aborting medication other than acetaminophen within 24 hours Allergy to metoclopramide, diphenhydramine, or codeine Systolic blood pressure >/= 140 Diastolic blood pressure >/= 90 History of brain tumor Active diagnosis of hyperemesis Acute asthma exacerbation at time of presentation Active labor

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Louis University	Saint Louis	Missouri	United States	63117

Sponsors and Collaborators

• St. Louis University

Investigators

• Principal Investigator: Dorothea Mostello, MD, St. Louis University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dorothea Mostello, MD, MD, St. Louis University
• ClinicalTrials.gov Identifier: NCT02295280
• Other Study ID Numbers: 15742
• First Posted: Nov 20, 2014
• Last Update Posted: Apr 2, 2018
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Dorothea Mostello, MD, MD, St. Louis University: headache
• Additional relevant MeSH terms: Headache; Diphenhydramine; Promethazine; Codeine; Metoclopramide

Study Results

Participant Flow

Recruitment Details	This was a prospective randomized, controlled trial at a single perinatal care center, conducted from December 2012 through September 2014 and approved by the IRB at Saint Louis University.

Arm/Group Title	Metoclopramide IV & Diphenhydramine IV	Codeine
Arm/Group Description	Intravenous (IV) access will be obtained and administration of 10mg Metoclopramide IV and 25mg Diphenhydramine IV Group A Metoclopramide: IV Diphenhydramine: iv	Group B (control group) will receive standard treatment consisting of a codeine 30mg tablet. Codeine: PO
Period Title: Overall Study
STARTED	35	35
COMPLETED	35	34
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Metoclopramide IV & Diphenhydramine IV	Codeine	Total
Arm/Group Description	Normotensive pregnant women in the second or third trimester were randomized to receive either MAD intravenously (10 mg and 25 mg, respectively) or codeine (30 mg) for headache symptoms after 650-1000 mg of acetaminophen failed to relieve the headache.	Normotensive pregnant women in the second or third trimester were randomized to receive either MAD intravenously (10 mg and 25 mg, respectively) or codeine (30 mg) for headache symptoms after 650-1000 mg of acetaminophen failed to relieve the headache.	Total of all reporting groups
Overall Participants	35	34	69
Age, Customized (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	35 100%	34 100%	69 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	23	23.5	23
Sex: Female, Male (Count of Participants)
Female	35 100%	34 100%	69 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	35 100%	34 100%	69 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adequate Relief of Headache as a Measure of Efficacy
Description	Number of participants with reduction in pain scores six hours post administration by at least 2 on the pain score scale.
Time Frame	Primary outcome was six hours post administration

Outcome Measure Data

Analysis Population Description

Number in each arm with data at 6 hours who received either metoclopramide and diphenhydramine IV or codeine.

Arm/Group Title	Metoclopramide IV & Diphenhydramine IV	Codeine
Arm/Group Description	Number of patients who received Metoclopramide & diphenhydramine IV	Number of patients who received codeine
Measure Participants	34	32
Count of Participants [Participants]	34 97.1%	32 94.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Metoclopramide IV & Diphenhydramine IV, Codeine
	Comments	A sample size calculation of 35 patients in each group was based on an estimated reduction in headache pain score by at least two points, with an a of 0.05 and power of 90%, which is similar to estimates reported in prior studies in non-pregnant patients and felt to be a clinically significant decrease. Statistical analyses were performed using chi-square, Fisher's exact test for categorical variables, the independent Student's t-test and Kolmogorov-Smirnov for continuous variables.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	Reduction in pain scores by at least 2 units six hours post administration
	Method	Mann Whitney U test
	Comments	Mann Whitney U test used for analysis of this continuous variable as data were not normally distributed. Outcome was comparable at the 6-hour mark.

Adverse Events

Time Frame	24 hours
Adverse Event Reporting Description	No SAEs
Arm/Group Title	Metoclopramide & Diphenhydramine		Codeine
Arm/Group Description	Participants received intravenous metoclopramine (10 mg) and diphenhydramine (25 mg), up to two doses of each medication.		Participants received oral 30 mg of oral codeine (up to two doses).
All Cause Mortality
	Metoclopramide & Diphenhydramine		Codeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Serious Adverse Events
	Metoclopramide & Diphenhydramine		Codeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	Metoclopramide & Diphenhydramine		Codeine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)

Limitations/Caveats

One of the limitations of our study is that codeine was used as standard for comparison to the MAD regimen. This was due to poor patient enrollment with an earlier study design comparing MAD to placebo.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.