Comparison of Gabapentin and Metoclopramide for Treating Hyperemesis Gravidarum

• Sponsor: University at Buffalo (Other)
• Overall Status: Completed
• CT.gov ID: NCT02163434
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 31
• Locations: 2
• Arms: 2
• Duration (Months): 65
• Patients Per Site: 15.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The investigators will compare the effectiveness of gabapentin to metoclopramide for 1 week among 60 women with hyperemesis gravidarum (HG) in this randomized, double-blinded trial. After completion of the 1-week double-blind phase, subjects will be offered open-label gabapentin with rescue metoclopramide until their symptoms no longer require treatment. Enrollment will occur at the University's at Buffalo, of Rochester and of Wisconsin.

Condition or Disease	Intervention/Treatment	Phase
Hyperemesis Gravidarum	Drug: Gabapentin; Drug: Metoclopramide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Comparison of Gabapentin and Metoclopramide for Treating Hyperemesis Gravidarum
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Oct 1, 2019
• Actual Study Completion Date: Nov 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: gabapentin 1800-2400mg/day divided tid or qid, orally.	Drug: Gabapentin; Other Names: Neurontin
Experimental: metoclopramide 45-60mg/day divided tid or qid, orally	Drug: Metoclopramide; Other Names: Reglan

Outcome Measures

Primary Outcome Measures

1. Baseline Adjusted Mean Daily Motherisk-PUQE Total Scores (Pregnancy-unique Quantification of Emesis and Nausea Scale) for Days 5-7 [1 week]

   Score range: 6-30 with higher score indicating a worse outcome.

Secondary Outcome Measures

1. Baseline Adjusted Mean Daily Nausea Scores From the Motherisk-PUQE for Days 5-7. [1 week]

   Score range: 2-10 with higher score indicating a worse outcome.

2. Baseline Adjusted Mean Daily Oral Nutrition Score for Days 5-7 [1 week]

   Score range: 0-15 with higher score indicating a better outcome.

3. Percent of Subjects Requiring Repeat iv Hydration or Hospital Admission for HG From the Outpatient Setting. [1 week]

4. Global Satisfaction of Treatment at the Study Endpoint. [1 week]

   Score range: 0-4 with higher score indicating a better outcome.

5. Desire to Continue Therapy at Study Endpoint [1 week]

   Scores: 0=no, 1=yes. Thus, a higher score indicates a better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Have received at least 2 administrations of intravenous (iv) hydration separated by at least 1 week or daily emesis for at least the last 14 days and 1 administration of iv hydration.

2. Have at least one of the following: 2-4+ ketonuria, serum potassium < 3.4mmol, or >5% weight loss from weight upon entry to prenatal care.

3. Have failed therapy with at least one antiemetic.

4. Have fetal ultrasound within 6 weeks prior to enrollment confirming a normal-appearing, intrauterine, singleton pregnancy of gestational age < 16 weeks at time of enrollment.

5. Felt by the patient's obstetrician or emergency room attending physician not to have other medical problems such as bowel obstruction, pancreatitis, biliary colic, or peptic ulcer disease that could be contributing to the patient's symptoms.

6. Be >18 years old and not decided to terminate the pregnancy.

7. Have not received or planning to receive a peripherally inserted central catheter (PIC line).

8. Have a Motherisk-PUQE score of ≥12 for the 24-hour Baseline period.

9. Felt not to have any other significant medical, psychiatric or substance abuse problem that would preclude participation in the study.

10. Denies drinking any alcohol after learning about current pregnancy.

11. Agrees to discontinue any current anti-emetic treatments (including antihistamines, ginger, > 10mg/day vitamin B6, serotonin or dopamine antagonists, anticholinergics, acupuncture, hypnosis, or wrist bands) for the next 4 weeks.

12. Pregnancy not conceived through in-vitro fertilization.

13. Able to understand and comply with the study procedures and give informed consent.

Exclusion Criteria:

None not mentioned under Inclusion Criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University at Buffalo	Buffalo	New York	United States	14214
2	University of Rochester	Rochester	New York	United States	14642

Sponsors and Collaborators

• University at Buffalo
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 2, 2016

More Information

Publications

• Guttuso T Jr, Robinson LK, Amankwah KS. Gabapentin use in hyperemesis gravidarum: a pilot study. Early Hum Dev. 2010 Jan;86(1):65-6. doi: 10.1016/j.earlhumdev.2009.11.003. Epub 2009 Dec 16.
• Guttuso T Jr. Gabapentin's anti-nausea and anti-emetic effects: a review. Exp Brain Res. 2014 Aug;232(8):2535-9. doi: 10.1007/s00221-014-3905-1. Epub 2014 Mar 26. Review.
• Holmes LB, Hernandez-Diaz S. Newer anticonvulsants: lamotrigine, topiramate and gabapentin. Birth Defects Res A Clin Mol Teratol. 2012 Aug;94(8):599-606. doi: 10.1002/bdra.23028. Epub 2012 Jun 22.

• Responsible Party: Thomas Guttuso, Associate Professor of Neurology, Obstetrics & Gynecology, University at Buffalo
• ClinicalTrials.gov Identifier: NCT02163434
• Other Study ID Numbers: 496486-3; 1R01HD076313-01A1
• First Posted: Jun 13, 2014
• Last Update Posted: Sep 27, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Thomas Guttuso, Associate Professor of Neurology, Obstetrics & Gynecology, University at Buffalo: pregnancy; nausea; vomiting; hyperemesis; treatment; gabapentin; metoclopramide; safety
• Additional relevant MeSH terms: Hyperemesis Gravidarum; Gabapentin; Metoclopramide

Study Results

Participant Flow

Arm/Group Title	Gabapentin	Metoclopramide
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin	45-60mg/day divided tid or qid, orally Metoclopramide
Period Title: Overall Study
STARTED	15	16
COMPLETED	12	9
NOT COMPLETED	3	7

Baseline Characteristics

Arm/Group Title	Gabapentin	Metoclopramide	Total
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin	45-60mg/day divided tid or qid, orally Metoclopramide	Total of all reporting groups
Overall Participants	12	9	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.2 (5.9)	26.3 (3.9)	26.25 (4.5)
Sex: Female, Male (Count of Participants)
Female	12 100%	9 100%	21 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
non-Hispanic white	2 16.7%	2 22.2%	4 19%
non-Hispanic black	10 83.3%	6 66.7%	16 76.2%
Hispanic white	0 0%	1 11.1%	1 4.8%
Region of Enrollment (participants) [Number]
United States	12 100%	9 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Baseline Adjusted Mean Daily Motherisk-PUQE Total Scores (Pregnancy-unique Quantification of Emesis and Nausea Scale) for Days 5-7
Description	Score range: 6-30 with higher score indicating a worse outcome.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Metoclopramide
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin	45-60mg/day divided tid or qid, orally Metoclopramide
Measure Participants	12	9
Mean (Standard Error) [units on a scale]	6.35 (2.44)	13.22 (2.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Metoclopramide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Baseline Adjusted Mean Daily Nausea Scores From the Motherisk-PUQE for Days 5-7.
Description	Score range: 2-10 with higher score indicating a worse outcome.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Metoclopramide
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin	45-60mg/day divided tid or qid, orally Metoclopramide
Measure Participants	12	9
Mean (Standard Error) [units on a scale]	2.01 (0.45)	3.69 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Metoclopramide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Baseline Adjusted Mean Daily Oral Nutrition Score for Days 5-7
Description	Score range: 0-15 with higher score indicating a better outcome.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Metoclopramide
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin	45-60mg/day divided tid or qid, orally Metoclopramide
Measure Participants	12	9
Mean (Standard Error) [units on a scale]	7.86 (1.23)	4.01 (1.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Metoclopramide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Percent of Subjects Requiring Repeat iv Hydration or Hospital Admission for HG From the Outpatient Setting.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Metoclopramide
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin	45-60mg/day divided tid or qid, orally Metoclopramide
Measure Participants	12	9
Count of Participants [Participants]	5 41.7%	5 55.6%

5. Secondary Outcome

Title	Global Satisfaction of Treatment at the Study Endpoint.
Description	Score range: 0-4 with higher score indicating a better outcome.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Metoclopramide
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin	45-60mg/day divided tid or qid, orally Metoclopramide
Measure Participants	12	9
Mean (Standard Error) [units on a scale]	2.22 (1.56)	0.63 (0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Metoclopramide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Desire to Continue Therapy at Study Endpoint
Description	Scores: 0=no, 1=yes. Thus, a higher score indicates a better outcome.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Metoclopramide
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin	45-60mg/day divided tid or qid, orally Metoclopramide
Measure Participants	12	9
Mean (Standard Error) [units on a scale]	0.67 (0.50)	0.14 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin, Metoclopramide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	1 week of double-blind therapy
Arm/Group Title	Gabapentin		Metoclopramide
Arm/Group Description	1800-2400mg/day divided tid or qid, orally. Gabapentin		45-60mg/day divided tid or qid, orally Metoclopramide
All Cause Mortality
	Gabapentin		Metoclopramide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/9 (0%)
Serious Adverse Events
	Gabapentin		Metoclopramide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Gabapentin		Metoclopramide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)		3/16 (18.8%)
Cardiac disorders
Tachycardia	1/15 (6.7%)	1	0/16 (0%)	0
Endocrine disorders
Hot Flashes	1/15 (6.7%)	1	0/16 (0%)	0
Gastrointestinal disorders
Diarrhea	0/15 (0%)	0	1/16 (6.3%)	1
Abdominal Pain	0/15 (0%)	0	1/16 (6.3%)	1
General disorders
fatigue	2/15 (13.3%)	2	0/16 (0%)	0
Nervous system disorders
Dizziness	1/15 (6.7%)	1	1/16 (6.3%)	1
Headache	0/15 (0%)	0	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

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.