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Study Title and Description

Metoclopramide and Diphenhydramine: A Randomized Controlled Trial of a Treatment for Headache in Pregnancy when Acetaminophen Alone Is Ineffective (MAD Headache Study).



Key Questions Addressed
2 Direct Evidence (Primary Studies): KQ 2 - What are the (comparative) benefits and harms of interventions to treat acute attacks of primary headache in women who are pregnant (or attempting to become pregnant), postpartum, or breastfeeding?
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Primary Publication Information
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TitleData
Title Metoclopramide and Diphenhydramine: A Randomized Controlled Trial of a Treatment for Headache in Pregnancy when Acetaminophen Alone Is Ineffective (MAD Headache Study).
Author Childress KMS., Dothager C., Gavard JA., Lebovitz S., Laska C., Mostello DJ.
Country Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Women's Health, Saint Louis University School of Medicine, St. Louis, Missouri.
Year 2018
Numbers Pubmed ID: 29723901

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Extraction form for Direct Evidence (Primary Studies)
Arms
Number Title Description Comments
1 Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine
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2 Opioid-containing Analgesics: Codeine
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Design Details
Question... Follow Up Answer Follow-up Answer
Which KEY QUESTION (KQ) does this study address? KQ2: Treatment of primary headache
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KQ2: Treatment of primary headache
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KQ2: Treatment of primary headache
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What is the STUDY DESIGN? Randomized controlled trial (RCT).....Skip to Question 5
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In what COUNTRY was the study done? US
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US
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US
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What was the FUNDING SOURCE of the study? Explicitly reported that the study was not funded.
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Explicitly reported that the study was not funded.
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Explicitly reported that the study was not funded.
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Does the study have a NAME or ACRONYM? ... Yes, specify... ... MAD Headache Study
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Does the study have a CLINICALTRIALS.GOV IDENTIFICATION NUMBER? ... Yes, specify the NCT number ("include NCT")... ... NCT02295280
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What were the START and END YEARS of the study? 2013
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2014
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What were the study INCLUSION criteria? Normotensive, 2nd/3rd trimester, acute or tension-type primary headache not relieved by 650 to 1,000 mg of acetaminophen
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What were the study EXCLUSION criteria? <16 years of age, received a headache treatment medication other than acetaminophen in the previous 24 hours
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Do you have any NOTES regarding the design or any overall aspects of this study?
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Baseline Characteristics
Question Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Total Comments
AnswerFollow-up AnswerFollow-up AnswerFollow-up
What was the SAMPLE SIZE at baseline? 35 35 70
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What were the RACE/ETHNICITY of the women in the study? White...% 20 White...% 28.6 Not reported
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Black...% 80 Black...% 71.4
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What was the AGE DISTRIBUTION of the women in the study? (CONTINUOUS data) Median 23 Median 23.5 Median 23
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IQR 21, 25 IQR 21, 27 IQR 21, 27
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What was the AGE DISTRIBUTION of the women in the study? (CATEGORICAL data) No data entered.
In what PHASE were the women in the study? 2nd trimester...% NR 2nd trimester...% NR Not reported...%
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3rd trimester...% NR 3rd trimester...% NR
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What was the GESTATIONAL AGE DISTRIBUTION of the women in the study? (CONTINUOUS data) Median 31.9 Median 28.4 Not reported
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IQR 25.7, 34.6 IQR 19.1, 32.9
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What was the UNIT for the gestational age you answered in the previous question? Weeks Weeks
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What was the GRAVIDITY DISTRIBUTION of the women in the study? (CONTINUOUS data) Median 3 Median 3 Not reported
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IQR 1, 4 IQR 2, 4
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What was the PARITY DISTRIBUTION of the women in the study? (CONTINUOUS data) Median 1 Median 1 Not reported
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IQR 0, 2 IQR 1, 2
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What were the TYPES of PRIMARY HEADACHE in the women in the study? Tension headache...% NR Tension headache...% NR Not reported...%
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Other...% Acute - NR Other...% Acute - NR
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What percentage of the women in the study had a HISTORY OF PRIMARY HEADACHE? Any primary headache...% 60.0 Any primary headache...% 42.9 Not reported
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Migraine 11.4 Migraine 14.3
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Do you have any NOTES regarding the baseline characteristics in this study? No data entered.



Results & Comparisons


Results Data
P-Value
Outcome: Acute headache attacks - Occurrence      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


24 hours

N Analyzed 34 32 0.14
Counts 13 19
Percentage 38.2 59.4
P-Value
Outcome: Adverse events - Maternal - "Non-serious"      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


24 hours

N Analyzed 34 32 0.41
Counts 15 10
Percentage 44.1 31.3
P-Value
Outcome: Acute headache attacks - Resolution      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


0 N/A

N Analyzed 34 32 <0.05
Counts 32 22
Percentage 94.1 68.8
P-Value
Outcome: Acute headache attacks - Resolution      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


0 N/A

N Analyzed 34 32 0.48
Counts 2 4
Percentage 5.9 12.5
P-Value
Outcome: Acute headache attacks - Resolution      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


24 hours

N Analyzed 34 32 <0.01
Counts 26 12
Percentage 76.5 37.5
P-Value
Outcome: Medication use      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


24 hours

N Analyzed 32 32 0.28
Counts 7 12
Percentage 21.9 37.5
P-Value
Outcome: Acute headache attacks - Severity      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


24 hours

N Analyzed 34 32 0.14
Counts 34 32
Percentage 100 100
Outcome: Adverse events - Maternal - Serious      Population: All Participants
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine


24 hours

N Analyzed 34 32
Counts 0 0
Percentage 0 0
P-Value P-Value P-Value P-Value P-Value P-Value
Outcome: Acute headache attacks - Severity      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


30 minutes

N Analyzed 35 35 <0.001
Mean 3.0 5.8
SD 2.8 2.3


1 hours

N Analyzed 35 35 <0.01
Mean 2.2 4.1
SD 2.3 3.0


6 hours

N Analyzed 33 32 0.14
Mean 1.8 2.5
SD NR NR


12 hours

N Analyzed 33 31 <0.05
Mean 1.3 2.7
SD 2.5 3.0


24 hours

N Analyzed 34 32 0.52
Mean 2.1 2.9
SD NR NR


0 minutes

N Analyzed 35 35 0.61
Mean 7.6 7.4
SD NR NR
P-Value
Outcome: Acute headache attacks - Resolution      Population: All Participants Between-Arm Comparisons
Time Point Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine Opioid-containing Analgesics: Codeine Comparison Measure Combination of Antiemetics: Metocolopromide and Antihistamines: Diphenydramine vs. Opioid-containing Analgesics: Codeine


24 hours

N Analyzed 35 35 <0.001
Mean 20.2 62.4
SD 13.4 62.2


Quality Dimensions
Dimension Value Notes Comments
Q1: ROBINS-I 1.1 Is there potential for confounding of the effect of intervention in this study?
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Q2: Did the study divide the follow up time of each individual participant into the different interventions?
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Q3: ROBINS-I 1.4. Did the authors use an appropriate analysis method that controlled for all the important confounding domains?
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Q4: ROBINS-I 1.5. If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?
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Q5: ROBINS-I 1.6. Did the authors control for any post-intervention variables that could have been affected by the intervention?
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Q6: Risk of bias judgement for BIAS DUE TO CONFOUNDING
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Q7: ROBINS-I 2.1. Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?
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Q8: ROBINS-I 2.2. If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?
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Q9: ROBINS-I 2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?
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Q10: ROBINS-I 2.4. Do start of follow-up and start of intervention coincide for most participants?
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Q11: Did the start and follow up calendar years coincide for most participants in the study?
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Q12: ROBINS-I 2.5. If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?
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Q13: ROBINS-I - Risk of bias judgement for BIAS IN SELECTION OF PARTICIPANTS INTO THE STUDY
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Q14: Cochrane - Random sequence generation (selection bias): Selection bias (biased allocation to interventions) due to inadequate generation of a randomized sequence Low computer-generated randomization sequence
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Q15: Cochrane - Allocation concealment (selection bias): Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment Low concealed in sequentially numbered opaque envelopes until patient enrollment
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Q16: Cochrane - Blinding of participants (performance bias): Performance bias due to knowledge of the allocated interventions by participants during the study High Open label trial
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Q17: Cochrane - Blinding of personnel/ care providers (performance bias): Performance bias due to knowledge of the allocated interventions by personnel/care providers during the study. High Open label trial
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Q18: Cochrane - FOR OBJECTIVE OUTCOMES - Blinding of outcome assessor (detection bias): Detection bias due to knowledge of the allocated interventions by outcome assessors. High Open label trial
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Q19: Cochrane - FOR SUBJECTIVE OUTCOMES - Blinding of outcome assessor (detection bias): Detection bias due to knowledge of the allocated interventions by outcome assessors. High Participants were not blinded
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Q21: Cochrane - Selective Reporting (reporting bias): Reporting bias due to selective outcome reporting High Primary outcome not reported adequately
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Q20: Cochrane - Incomplete outcome data (attrition bias): Attrition bias due to amount, nature or handling of incomplete outcome data Low Less than 20% loss to followup
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Q22: Cochrane - Other Bias: Bias due to problems not covered elsewhere in the table. If yes, describe them in the Notes. Low No other relevant biases
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Q23: NHLBI - Were eligibility/selection criteria for the study population prespecified and clearly described? Yes
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Q24: NHLBI - Was the test/service/intervention clearly described and delivered consistently across the study population? Yes
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Q25: NHLBI - Were the outcome measures prespecified, clearly defined, valid, reliable, and assessed consistently across all study participants? Yes
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Quality Rating
No quality rating data was found.