Furosemide vs Placebo in Severe Preeclampsia Postpartum (FUROPE)

Furosemide Oral Versus Placebo for Reduction of Hospital Length of Stay in Postpartum Women With Severe Preeclampsia: A Double-Blind, Randomized Controlled Trial

This randomized, double-blind, placebo-controlled trial evaluates whether oral furosemide 40 mg, initiated 12 hours postpartum, reduces hospital length of stay compared to placebo (folic acid 5 mg) in postpartum women with severe preeclampsia. Secondary outcomes include need for rescue antihypertensive medications, weight reduction, and metabolic safety (hypokalemia, renal function). A total of 186 participants (93 per arm) will be enrolled across two hospitals in Honduras.

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Preeclampsia
• Intervention / Treatment: Drug: Furosemide; Drug: Folic Acid 5 MG

Detailed Description

Background: Preeclampsia is a leading cause of maternal morbidity worldwide. Postpartum management focuses on blood pressure control and resolution of endothelial dysfunction. Loop diuretics like furosemide may accelerate normalization of intravascular volume and blood pressure, potentially reducing hospital stay.

Hypothesis: Furosemide 40 mg oral once daily reduces total postpartum hospital hours compared to placebo.

Study Design: Phase 2, randomized, double-blind, placebo-controlled, parallel-group trial.

Setting: Hospital Materno Infantil and Instituto Hondureño de Seguridad Social, Honduras.

Interventions:

Experimental: Furosemide 40 mg oral every 24 hours, starting at 12 hours postpartum, continued until hospital discharge.

Placebo: Folic acid 5 mg oral (identical appearance, packaging, and administration schedule).

Blinding: Double-blind. Only an independent pharmacist knows group assignment. Blinding is broken only for life-threatening adverse events.

Follow-up: Entirely inpatient, from enrollment (12 hours postpartum) until hospital discharge (estimated 3-7 days).

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ricardo A. Gutierrez-Ramirez, MD, MSc; Phone Number: +50497546940; Email: ricardo.gutierrez@unah.edu.hn

Study Locations

• Honduras
  • Francisco Morazán Department
    • Tegucigalpa, Francisco Morazán Department, Honduras, 11101
      • Hospital Escuela
      • Contact: Ricardo A. Gurierrez Ramirez, MD, MSc.; Phone Number: 97546940; Email: ricardo.gutierrez@unah.edu.hn
      • Principal Investigator: Francisco J. Salgado Turcios, MD
      • Principal Investigator: Andrés F. García Mejía, MD
      • Sub-Investigator: Doria A. Carrasco, MD, MSc.
      • Sub-Investigator: Sobeyda Lopez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent (assent for minors 14-17 years with parental/guardian consent)
• Confirmed severe preeclampsia (BP ≥160/110 mmHg, or lower BP with thrombocytopenia, hepatic dysfunction, renal insufficiency, pulmonary edema, or cerebral/visual symptoms)
• Postpartum (12-24 hours after delivery, vaginal or cesarean)
• Hemodynamically stable (no vasopressors for ≥6 hours)
• Preserved diuresis (>30 mL/hour for ≥6 hours)
• Serum creatinine <0.8 mg/dL

Exclusion Criteria:

• Current or chronic diuretic use (before or during pregnancy)
• Known allergy to sulfonamides or furosemide
• Active febrile illness
• Known chronic kidney disease (eGFR <60 mL/min/1.73m²)
• Participation in another interventional trial
• Pregnancy (current - not applicable postpartum, but excludes undiagnosed concurrent pregnancy)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furosemide; Every 24 hours starting at 12 hours postpartum until discharge	Drug: Furosemide; Furosemide 40 mg tablet, oral, once daily. First dose administered exactly 12 hours postpartum (vaginal or cesarean). Continued every 24 hours until hospital discharge, defined as blood pressure <140/90 mmHg for ≥24 hours without rescue antihypertensives. Population: severe preeclampsia (BP ≥160/110 mmHg OR lower BP with thrombocytopenia, hepatic dysfunction, renal insufficiency, pulmonary edema, or cerebral/visual symptoms). Setting: postpartum wards in two public hospitals in Honduras. Rescue medication: labetalol or hydralazine for BP >160/110 mmHg, deferred ≥2 hours after study drug when possible. Placebo comparator: folic acid 5 mg orally every 24 hours, identical appearance, packaging, and schedule. What distinguishes this intervention: first postpartum diuretic trial in severe preeclampsia with hospital length of stay as primary endpoint in a low-middle income country setting.
Placebo Comparator: Placebo; Folic acid, 5 mg per day Every 24 hours starting at 12 hours postpartum until discharge	Drug: Folic Acid 5 MG; Folic acid 5 mg oral once daily, starting at exactly 12 hours postpartum until hospital discharge (BP <140/90 mmHg for ≥24 hours without rescue drugs). Population: severe preeclampsia. Setting: public hospitals, Honduras. Rescue: labetalor hydralazine for BP >160/110 mmHg, deferred ≥2 hours post-dose. Active comparator: furosemide 40 mg oral, identical appearance and schedule. Folic acid has no antihypertensive or diuretic effects in postpartum women, serving as an appropriate placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Length of Stay (Hours)	Total hours from first study dose (administered at 12 hours postpartum) to hospital discharge. Discharge is defined as achievement and maintenance of blood pressure <140/90 mmHg for at least 24 consecutive hours without need for rescue antihypertensive medication. Rescue medication is defined as any extra dose of labetalol or hydralazine administered for hypertensive crisis (blood pressure >160/110 mmHg). Time is measured in hours from the moment of first dose (hour 0) until the moment discharge orders are written. If a patient requires rescue medication, the clock does not reset; discharge criteria must still be met for 24 hours without rescue.	From first study dose (12 hours postpartum) up to hospital discharge, approximately 3 to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion Requiring Rescue Antihypertensive Medication	Percentage of participants in each arm who require at least one dose of rescue antihypertensive medication (labetalol or hydralazine) during hospitalization. Rescue medication is indicated for hypertensive crisis defined as systolic blood pressure >160 mmHg or diastolic blood pressure >110 mmHg at any time after study drug administration. The proportion is calculated as number of participants receiving any rescue dose divided by total participants in the arm.	From first study dose (12 hours postpartum) until hospital discharge, approximately 3 to 14 days
Weight Reduction (Delta Weight in kg)	Absolute difference between baseline weight (measured at 12 hours postpartum, immediately before first study dose) and weight at hospital discharge (measured on the morning of discharge day). Weight is measured in kilograms using the same calibrated scale for each participant. Delta weight is calculated as baseline weight minus discharge weight. A positive value indicates weight loss.	Baseline (12 hours postpartum) and at hospital discharge (approximately 3 to 14 days later)
Incidence of Hypokalemia	Proportion of participants in each arm developing hypokalemia, defined as serum potassium <3.0 mEq/L. Blood sample is drawn at 48 hours after first study dose or at hospital discharge (whichever occurs first). Hypokalemia is considered an adverse event of special interest given furosemide's mechanism of action as a loop diuretic. Severe hypokalemia (<2.5 mEq/L) triggers unblinding and protocol-defined management.	At 48 hours after first study dose or at hospital discharge (approximately 3 to 14 days)
Renal Function Deterioration	Change in serum creatinine from baseline to follow-up measurement. Baseline creatinine is measured at enrollment (12 hours postpartum, before first dose). Follow-up creatinine is measured at 48 hours after first dose or at hospital discharge (whichever occurs first). Renal deterioration is defined as an increase in serum creatinine of ≥0.3 mg/dL from baseline or a percentage increase of ≥50%. Mean change (absolute and percentage) is compared between groups.	Baseline (12 hours postpartum) and at 48 hours or hospital discharge (approximately 3 to 14 days)
Spontaneously Reported Adverse Events	Incidence of spontaneously reported adverse events potentially related to furosemide, including dizziness/orthostatic hypotension, muscle cramps, and palpitations. Participants are asked daily "Have you experienced any unusual symptoms since the last dose?" Responses are recorded regardless of suspected relationship to study drug. Severity is graded as mild (minimal or no treatment needed), moderate (some interference with daily activities), or severe (significant interference).	From first study dose (12 hours postpartum) until hospital discharge, daily assessment, approximately 3 to 14 days
Antihypertensive-Free Discharge	Proportion of participants discharged from the hospital without requiring any maintenance antihypertensive medication. Maintenance antihypertensives are defined as scheduled oral medications (not rescue doses) intended to control blood pressure after discharge. Participants who require continued antihypertensive therapy at discharge (any dose, any agent) are considered not achieving antihypertensive-free discharge.	At hospital discharge, approximately 3 to 14 days after first study dose

Collaborators and Investigators

• Sponsor: Universidad Nacional Autonoma de Honduras

Publications and helpful links

General Publications

• Cursino T, Katz L, Coutinho I, de Souza ASR, Silva TV, Cunha ACCD, Amorim M. Postpartum furosemide for accelerating recovery in patients with preeclampsia: a randomized placebo-controlled trial. Am J Obstet Gynecol MFM. 2025 May;7(5):101614. doi: 10.1016/j.ajogmf.2025.101614. Epub 2025 Jan 25.

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 15, 2027

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Hypertension; Postpartum; Preeclampsia; Furosemide; Length of Stay
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Hypertension; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amides; Aniline Compounds; Amines; Pterins; Pteridines; Sulfonamides; Sulfanilamides; Sulfones; Folic Acid; Furosemide
• Other Study ID Numbers: PGO-UNAH-49-10-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data (IPD) for all primary and secondary outcome measures will be shared publicly via Mendeley Data repository. The dataset will include: participant demographics, baseline clinical characteristics, primary outcome (hospital length of stay in hours), secondary outcomes (rescue medication requirement, weight change, laboratory values including potassium and creatinine, adverse events, discharge antihypertensive status), and protocol deviations. Data will be anonymized with no direct identifiers (name, medical record number, date of birth). Each participant will be identified by a unique study code only.

Timeline: Data will be deposited within 12 months after primary results publication. The repository link will be included in the primary publication and in this ClinicalTrials.gov record when available.

Supporting documents also available via Mendeley Data: Study protocol (v1.0), Statistical Analysis Plan (SAP), and blank informed consent form

• IPD Sharing Time Frame: Available starting 12 months after primary results publication. Available for 5 years thereafter.
• IPD Sharing Access Criteria: No registration or authorization required for download. Data will be under a CC BY-NC 4.0 license (Creative Commons Attribution-NonCommercial 4.0 International), allowing other researchers to use, share, and adapt the data for non-commercial purposes with proper attribution.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

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