Cabergoline for Lactation Inhibition After Second-Trimester Abortion or Loss (LISTA)

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.

Study Overview

• Status: Completed
• Conditions: Lactation Suppressed
• Intervention / Treatment: Drug: Placebo; Drug: Cabergoline 1 MG

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant people, ages 18 years or older
• Intrauterine pregnancy between 18/0-28/0 weeks of gestation age (by ultrasound dating performed prior to or same day of enrollment visit)
• Consented for an induced, elective abortion or undergoing induction for demise
• English or Spanish speaking
• Able to consent for a research study, literate in English or Spanish
• Willing to comply with study procedures and follow-up
• Access to smart phone throughout study

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)

  • Uncontrolled hypertension - defined as baseline BP > 150/100, or chronic hypertension requiring more than one baseline medication, or pregnancy-induced hypertension spectrum disorders (gestational hypertension, preeclampsia, eclampsia)
  • History of cardiac valvular disorders or valvular repair
  • History of pulmonary, pericardial, or retroperitoneal fibrotic disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Cabergoline 1 MG; Dopamine agonist; Other Names: Dostinex
Placebo Comparator: 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.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Andrea Henkel, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): June 24, 2022
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: engorgement; lactation; abortion; intrauterine fetal demise; second-trimester
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Cabergoline
• Other Study ID Numbers: 58470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data may be requested for meta-analysis inclusion.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes