Hyperemesis Gravidarum
Conditions
Keywords
pregnancy, nausea, vomiting, hyperemesis, treatment, gabapentin, metoclopramide, safety
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.
Interventions
DRUGGabapentin
DRUGMetoclopramide
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
State University of New York at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Baseline Adjusted Mean Daily Oral Nutrition Score for Days 5-7 | 1 week | Score range: 0-15 with higher score indicating a better outcome. |
| Percent of Subjects Requiring Repeat iv Hydration or Hospital Admission for HG From the Outpatient Setting. | 1 week | — |
| Global Satisfaction of Treatment at the Study Endpoint. | 1 week | Score range: 0-4 with higher score indicating a better outcome. |
| Desire to Continue Therapy at Study Endpoint | 1 week | Scores: 0=no, 1=yes. Thus, a higher score indicates a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gabapentin 1800-2400mg/day divided tid or qid, orally.
Gabapentin | 12 |
| Metoclopramide 45-60mg/day divided tid or qid, orally
Metoclopramide | 9 |
| Total | 21 |
Baseline characteristics
| Characteristic | Metoclopramide | Gabapentin | Total |
|---|---|---|---|
| Age, Continuous | 26.3 years STANDARD_DEVIATION 3.9 | 26.2 years STANDARD_DEVIATION 5.9 | 26.25 years STANDARD_DEVIATION 4.5 |
| Race/Ethnicity, Customized Hispanic white | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized non-Hispanic black | 6 Participants | 10 Participants | 16 Participants |
| Race/Ethnicity, Customized non-Hispanic white | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 9 participants | 12 participants | 21 participants |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 21 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 9 |
| other Total, other adverse events | 4 / 15 | 3 / 16 |
| serious Total, serious adverse events | 0 / 12 | 0 / 9 |
Outcome results
Primary
Baseline Adjusted Mean Daily Motherisk-PUQE Total Scores (Pregnancy-unique Quantification of Emesis and Nausea Scale) for Days 5-7
Score range: 6-30 with higher score indicating a worse outcome.
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Baseline Adjusted Mean Daily Motherisk-PUQE Total Scores (Pregnancy-unique Quantification of Emesis and Nausea Scale) for Days 5-7 | 6.35 units on a scale | Standard Error 2.44 |
| Metoclopramide | Baseline Adjusted Mean Daily Motherisk-PUQE Total Scores (Pregnancy-unique Quantification of Emesis and Nausea Scale) for Days 5-7 | 13.22 units on a scale | Standard Error 2.39 |
p-value: 0.01Mixed Models Analysis
Secondary
Baseline Adjusted Mean Daily Nausea Scores From the Motherisk-PUQE for Days 5-7.
Score range: 2-10 with higher score indicating a worse outcome.
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Baseline Adjusted Mean Daily Nausea Scores From the Motherisk-PUQE for Days 5-7. | 2.01 units on a scale | Standard Error 0.45 |
| Metoclopramide | Baseline Adjusted Mean Daily Nausea Scores From the Motherisk-PUQE for Days 5-7. | 3.69 units on a scale | Standard Error 0.45 |
p-value: 0.005Mixed Models Analysis
Secondary
Baseline Adjusted Mean Daily Oral Nutrition Score for Days 5-7
Score range: 0-15 with higher score indicating a better outcome.
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Baseline Adjusted Mean Daily Oral Nutrition Score for Days 5-7 | 7.86 units on a scale | Standard Error 1.23 |
| Metoclopramide | Baseline Adjusted Mean Daily Oral Nutrition Score for Days 5-7 | 4.01 units on a scale | Standard Error 1.34 |
p-value: 0.01Mixed Models Analysis
Secondary
Desire to Continue Therapy at Study Endpoint
Scores: 0=no, 1=yes. Thus, a higher score indicates a better outcome.
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Desire to Continue Therapy at Study Endpoint | 0.67 units on a scale | Standard Error 0.5 |
| Metoclopramide | Desire to Continue Therapy at Study Endpoint | 0.14 units on a scale | Standard Error 0.38 |
p-value: 0.06Mixed Models Analysis
Secondary
Global Satisfaction of Treatment at the Study Endpoint.
Score range: 0-4 with higher score indicating a better outcome.
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Global Satisfaction of Treatment at the Study Endpoint. | 2.22 units on a scale | Standard Error 1.56 |
| Metoclopramide | Global Satisfaction of Treatment at the Study Endpoint. | 0.63 units on a scale | Standard Error 0.74 |
p-value: 0.03Mixed Models Analysis
Secondary
Percent of Subjects Requiring Repeat iv Hydration or Hospital Admission for HG From the Outpatient Setting.
Time frame: 1 week
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gabapentin | Percent of Subjects Requiring Repeat iv Hydration or Hospital Admission for HG From the Outpatient Setting. | 5 Participants |
| Metoclopramide | Percent of Subjects Requiring Repeat iv Hydration or Hospital Admission for HG From the Outpatient Setting. | 5 Participants |