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This research study investigates the use of a drug, cabergoline, given immediately after second-trimester abortion or perinatal loss to decrease breast engorgement. Cabergoline is a medication approved for the symptomatic treatment of pituitary adenomas that result in a hyperprolactinemic state (a brain tumor that results in milk leakage). The benefit of stopping milk leakage has also been studied and used in populations who shouldn't breastfeed. The investigators aim to clarify if cabergoline is effective in preventing breast engorgement and milk leakage after second-trimester abortions or perinatal loss (stillbirth). Breast engorgement causes physical pain and emotional distress as lactation is uniquely associated with parenthood and those undergoing second-trimester abortions are doing so because they choose not to parent or a previously desired pregnancy is now complicated by anomalies. As there are no current recommendations for management of this painful engorgement beyond icepacks and support bras, the investigators aim to validate the use of this pharmacologic option in this setting.
Breast pain following second-trimester abortion is common. Breast engorgement and milk leakage following second-trimester perinatal loss and abortion can cause both physical pain and emotional distress. Dopamine agonists have previously been shown to be effective in lactation inhibition for third-trimester fetal/neonatal loss or contraindications to breastfeeding. In a head-to-head trial, cabergoline was more effective with a better safety profile than bromocriptine and has thus emerged as preferred treatment for term lactation inhibition internationally. Despite the frequency of breast symptoms after second-trimester abortions, there are no current guidelines for this population.
The investigators are conducting a double-blinded, placebo-controlled, superiority trial of participants undergoing abortion or experiencing intrauterine fetal demise between 18 and 28-weeks gestation at Stanford Health Care. Participants will be randomized to either cabergoline 1mg or placebo the day of procedure. Participants will complete the Bristol Breast Inventory, a survey to assess symptoms and side-effects at baseline and day 2, 3, 4, 7, and 14 after the procedure.
The primary outcome is breast symptoms on Day 4 as reported on the Bristol Breast Inventory. Secondary outcomes include satisfaction, acceptability, and side-effects. Investigators hypothesize that cabergoline is superior to placebo for preventing breast engorgement after second-trimester abortion or loss. A sub-study of 6 participants will return for serum prolactin levels at baseline, days 4, 7, 14 after procedure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cabergoline | Experimental | After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered cabergoline 1mg orally with juice or water by the clinician or study investigator. |
|
| Placebo | Placebo Comparator | After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered a placebo pill orally with juice or water by the clinician or study investigator. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cabergoline 1 MG | Drug | Dopamine agonist |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting Breast Pain | Participants will assess their breast symptoms using the validated Bristol Breast Inventory survey to assess 4 domains of breast symptoms: tenderness, engorgement, leaking milk, pain relief. Participants who indicated symptoms in any of these areas met the criteria for this outcome. | Day 4 after procedure |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing Side-effects | Participants selected from previously documented side-effects from the dopaminergic class or free-text. Participants may have reported more than one side-effect. | 2 weeks |
| Number of Participants Reporting Significant Bother From Breast Pain |
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Inclusion Criteria:
Exclusion Criteria:
Prior mastectomy (breast reduction or chest masculinization surgery acceptable)
Currently breastfeeding
Currently receiving dopamine agonist therapy for other indication (prolactinoma, Cushings syndrome, acromegaly, restless leg syndrome)
Contraindication to cabergoline (as per package insert)
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37863161 | Derived | Henkel A, Reeves MF, Shaw KA. The experience of breast symptoms after second-trimester abortion or pregnancy loss. Am J Obstet Gynecol. 2024 Mar;230(3):e3-e5. doi: 10.1016/j.ajog.2023.10.025. Epub 2023 Oct 18. No abstract available. | |
| 37486652 | Derived | Henkel A, Johnson SA, Reeves MF, Cahill EP, Blumenthal PD, Shaw KA. Cabergoline for Lactation Inhibition After Second-Trimester Abortion or Pregnancy Loss: A Randomized Controlled Trial. Obstet Gynecol. 2023 Jun 1;141(6):1115-1123. doi: 10.1097/AOG.0000000000005190. Epub 2023 May 3. |
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De-identified data may be requested for meta-analysis inclusion.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cabergoline | After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered cabergoline 1mg orally with juice or water by the clinician or study investigator. Cabergoline 1 MG: Dopamine agonist |
| FG001 | Placebo | After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered a placebo pill orally with juice or water by the clinician or study investigator. Placebo: Placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cabergoline | After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered cabergoline 1mg orally with juice or water by the clinician or study investigator. Cabergoline 1 MG: Dopamine agonist |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Reporting Breast Pain | Participants will assess their breast symptoms using the validated Bristol Breast Inventory survey to assess 4 domains of breast symptoms: tenderness, engorgement, leaking milk, pain relief. Participants who indicated symptoms in any of these areas met the criteria for this outcome. | Participants who returned survey data for this outcome are included in the analysis. | Posted | Count of Participants | Participants | Day 4 after procedure |
|
From day of enrollment until 14 days after procedure
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cabergoline | After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered cabergoline 1mg orally with juice or water by the clinician or study investigator. Cabergoline 1 MG: Dopamine agonist |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Principal Investigator | Stanford University | 650-497-5175 | gynresearch@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 13, 2021 | Jan 9, 2024 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D050497 | Stillbirth |
| D001942 | Breast Feeding |
| D006940 | Hyperemia |
| ID | Term |
|---|---|
| D005313 | Fetal Death |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077465 | Cabergoline |
| ID | Term |
|---|---|
| D004873 | Ergolines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Placebo |
|
Assessed using a Facial Pain Score (scale range 0-6, significant bother >=4) |
| Day 4 after procedure |
| Serum Prolactin Level | A subset of participants returned blood tests to measure effectiveness of drug | Day 4 after procedure |
| Number of Participants Reporting Significant Bother From Side-effects | Assessed using a Facial Pain Score (scale range 0-6, significant bother >=4) | Day 4 after procedure |
| Placebo |
After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered a placebo pill orally with juice or water by the clinician or study investigator. Placebo: Placebo |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Gestational age at time of procedure | Mean | Standard Deviation | days |
|
| Nulliparous | Number | participants |
|
| Indication | Count of Participants | Participants |
|
| Placebo |
After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered a placebo pill orally with juice or water by the clinician or study investigator. Placebo: Placebo |
|
|
| Secondary | Number of Participants Experiencing Side-effects | Participants selected from previously documented side-effects from the dopaminergic class or free-text. Participants may have reported more than one side-effect. | Participants who returned survey data for this outcome are included in the analysis. | Posted | Count of Participants | Participants | 2 weeks |
|
|
|
| Secondary | Number of Participants Reporting Significant Bother From Breast Pain | Assessed using a Facial Pain Score (scale range 0-6, significant bother >=4) | Participants who returned survey data for this outcome are included in the analysis. | Posted | Count of Participants | Participants | Day 4 after procedure |
|
|
|
| Secondary | Serum Prolactin Level | A subset of participants returned blood tests to measure effectiveness of drug | Participants who returned for serum blood draws | Posted | Mean | Standard Deviation | ng/mL | Day 4 after procedure |
|
|
|
| Secondary | Number of Participants Reporting Significant Bother From Side-effects | Assessed using a Facial Pain Score (scale range 0-6, significant bother >=4) | Participants who returned survey data for this outcome are included in the analysis. | Posted | Count of Participants | Participants | Day 4 after procedure |
|
|
|
| 0 |
| 36 |
| 0 |
| 36 |
| 0 |
| 36 |
| EG001 | Placebo | After the completion of the surgical procedure or medical induction for the second-trimester abortion or fetal loss, the participant will be administered a placebo pill orally with juice or water by the clinician or study investigator. Placebo: Placebo | 0 | 37 | 0 | 37 | 0 | 37 |
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| D003643 | Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D005247 | Feeding Behavior |
| D001519 | Behavior |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006576 |
| Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Dizziness/ lightheadness |
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| Constipation |
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| Acid reflux |
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| Fatigue |
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| Lower extremity edema |
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| Hot flashes |
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| Palpitations |
|
| Anxiety |
|
| Insomnia |
|
| Visual disturbance |
|