Severe Preeclampsia
Conditions
Keywords
Preeclampsia, Furosemide, Postpartum, Hypertension, Length of Stay
Brief summary
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.
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).
Interventions
DRUGFurosemide
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.
DRUGFolic 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.
Sponsors
Universidad Nacional Autonoma de Honduras
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
1. Participants - Patients receive identical opaque white bottles labeled only with "Estudio FURO-PE, Paciente #XXX" and have no knowledge of whether the contents are furosemide 40 mg or placebo (folic acid 5 mg). 2. Investigators (Principal Investigators and Sub-investigators) - All clinical staff responsible for enrollment, outcome assessment, and discharge decisions are unaware of group assignment. 3. Outcome assessors - The same research team members who evaluate blood pressure, laboratory results, and discharge criteria are masked. 4. Statistician - The data analyst will receive a dataset with group codes (A/B) and will not know which code corresponds to furosemide or placebo until final database lock. Only one independent, unblinded person (a designated pharmacist not involved in patient care or outcome assessment) knows the allocation. This person prepares and labels all bottles but does not interact with participants or investigators.
Intervention model description
Double-blind (participant, investigator, outcomes assessor)
Eligibility
Sex/Gender
FEMALE
Age
14 Years to 49 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay (Hours) | From first study dose (12 hours postpartum) up to hospital discharge, approximately 3 to 14 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion Requiring Rescue Antihypertensive Medication | From first study dose (12 hours postpartum) until hospital discharge, approximately 3 to 14 days | 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. |
| Weight Reduction (Delta Weight in kg) | Baseline (12 hours postpartum) and at hospital discharge (approximately 3 to 14 days later) | 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. |
| Incidence of Hypokalemia | At 48 hours after first study dose or at hospital discharge (approximately 3 to 14 days) | 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. |
| Renal Function Deterioration | Baseline (12 hours postpartum) and at 48 hours or hospital discharge (approximately 3 to 14 days) | 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. |
| Spontaneously Reported Adverse Events | From first study dose (12 hours postpartum) until hospital discharge, daily assessment, approximately 3 to 14 days | 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). |
| Antihypertensive-Free Discharge | At hospital discharge, approximately 3 to 14 days after first study dose | 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. |
Countries
Honduras
Contacts
CONTACTRicardo A. Gutierrez-Ramirez, MD, MSc
Outcome results
None listed