Furosemide vs. Placebo for Severe Antepartum Hypertension

NCT04615624 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 2020-003
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective: To determine whether the addition of intravenous furosemide with usual antihypertensives is associated with a reduction in mean systolic blood pressure from baseline compared to treatment with placebo plus usual antihypertensives (intravenous labetalol, intravenous hydralazine, or oral immediate release nifedipine) for the management of severe antepartum hypertension. Secondary objectives: To determine whether the addition of intravenous furosemide with usual antihypertensives is associated with a reduction in mean diastolic blood pressure compared to treatment with placebo plus usual antihypertensives listed above.

Conditions

Pre-Eclampsia; Hypertension in Pregnancy; Pregnancy Complications; Hypertension, Pregnancy-Induced

Keywords

Severe range blood pressure; Pre-eclampsia; Gestational hypertension; Wide pulse pressure; High-risk pregnancy; Pregnancy complications

Outcome Measures

Primary Outcomes (1)

• Mean Systolic Blood Pressure During Hour After Study Drug

  Mean systolic blood pressure during hour after study drug administration.

  0 minutes to 60 minutes post-dose

Secondary Outcomes (6)

• Mean Diastolic Blood Pressure During Hour After Study Drug

  0 minutes to 60 minutes post-dose

• Change From Qualifying Systolic Blood Pressure

  0 minutes to 1 hour post-dose

• Change From Qualifying Diastolic Blood Pressure

  0 minutes to 1 hour post-dose

• Pulse Pressure at 2 Hours After Study Drug.

  2 hours post-dose

• Systolic Blood Pressure at 2 Hours After Study Drug

  2 hours post-dose

Other Outcomes (14)

• Gestational Age at Delivery

  at the time of birth

• Time From Admission to Delivery

  at the time of delivery

• Time From Treatment to Delivery

  at the time of delivery

Study Arms (2)

Furosemide

EXPERIMENTAL

When patient meets inclusion criteria and is randomized to treatment drug, she receives 40mg /4 milliliters (mL) IV furosemide in addition to usual antihypertensive.

Drug: Furosemide

Placebo

PLACEBO COMPARATOR

When patient meets inclusion criteria and is randomized to placebo, she receives one dose of 4mL normal saline in addition to usual antihypertensive.

Other: Placebo

Interventions

Furosemide DRUG

Furosemide, a loop diuretic

Furosemide

Placebo OTHER

Normal saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects 18 years of age or older
• Subjects with intrauterine pregnancy at or beyond 20 weeks of gestation
• Subjects with a diagnosis of hypertensive disorder in pregnancy
• Subjects with persistent (on repeat BP check 15 min apart) severe range blood pressure recordings (systolic BP greater than or equal to 160 or diastolic greater than or equal to BP 110) with wide pulse pressure (\>60 mmHg)
• Subject able to provide informed consent

You may not qualify if:

• Subjects less than 18 years of age
• Subjects with intrauterine pregnancy less than 20 weeks of gestation
• Subjects with known fetal anomaly
• Subjects with hypokalemia (K \<3.0 milliequivalent per liter) on admission
• Subjects with anuria (\<50 milliliters urine in 24 hours) or renal failure
• Subjects previously taking diuretics or potassium supplements for any reason
• Subjects with a known allergy/adverse reaction to furosemide
• Subjects who are unable to understand and/or sign the informed consent
• Subjects who are in active labor defined as 6 centimeters of cervical dilation or more
• Subjects who have an epidural (neuraxial anesthesia) in place

Sponsors & Collaborators

• Melanie Maykin, MD: lead

Study Sites (1)

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Related Publications (10)

• Grindheim G, Estensen ME, Langesaeter E, Rosseland LA, Toska K. Changes in blood pressure during healthy pregnancy: a longitudinal cohort study. J Hypertens. 2012 Feb;30(2):342-50. doi: 10.1097/HJH.0b013e32834f0b1c.

  PMID: 22179091 BACKGROUND

• Phillips JK, Janowiak M, Badger GJ, Bernstein IM. Evidence for distinct preterm and term phenotypes of preeclampsia. J Matern Fetal Neonatal Med. 2010 Jul;23(7):622-6. doi: 10.3109/14767050903258746.

  PMID: 20482241 BACKGROUND

• Easterling TR, Benedetti TJ, Schmucker BC, Millard SP. Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol. 1990 Dec;76(6):1061-9.

  PMID: 2234714 BACKGROUND

• ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstet Gynecol. 2019 Jan;133(1):1. doi: 10.1097/AOG.0000000000003018.

  PMID: 30575675 BACKGROUND

• https://www.uptodate.com/contents/furosemide-drug information?search=furosemide&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1

  BACKGROUND

• Tamas P, Hantosi E, Farkas B, Ifi Z, Betlehem J, Bodis J. Preliminary study of the effects of furosemide on blood pressure during late-onset pre-eclampsia in patients with high cardiac output. Int J Gynaecol Obstet. 2017 Jan;136(1):87-90. doi: 10.1002/ijgo.12019. Epub 2016 Nov 3.

  PMID: 28099709 BACKGROUND

• Ascarelli MH, Johnson V, McCreary H, Cushman J, May WL, Martin JN Jr. Postpartum preeclampsia management with furosemide: a randomized clinical trial. Obstet Gynecol. 2005 Jan;105(1):29-33. doi: 10.1097/01.AOG.0000148270.53433.66.

  PMID: 15625138 BACKGROUND

• Duley L, Meher S, Jones L. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2013 Jul 31;2013(7):CD001449. doi: 10.1002/14651858.CD001449.pub3.

  PMID: 23900968 BACKGROUND

• Committee on Obstetric Practice. Committee Opinion No. 692: Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. Obstet Gynecol. 2017 Apr;129(4):e90-e95. doi: 10.1097/AOG.0000000000002019.

  PMID: 28333820 BACKGROUND

• Maykin MM, Mercer E, Saiki KM, Kaneshiro B, Miller CB, Tsai PS. Furosemide to lower antenatal severe hypertension: a randomized placebo-controlled trial. Am J Obstet Gynecol MFM. 2024 Apr;6(4):101348. doi: 10.1016/j.ajogmf.2024.101348. Epub 2024 Mar 12.

  PMID: 38485054 DERIVED

MeSH Terms

Conditions

Pre-Eclampsia; Hypertension, Pregnancy-Induced; Pregnancy Complications

Interventions

Furosemide

Condition Hierarchy (Ancestors)

Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Melanie Maykin
• Organization: University of Hawaii and Hawaii Pacific Health

mmaykin@hawaii.edu

8089836000

Study Officials

• Stacy Tsai, MD

  Maternal-Fetal Medicine Faculty

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: After informed consent and upon meeting inclusion criteria, the study personnel will inform pharmacy personnel who will then randomly assigned the patient to groups by opening the next previously prepared sequential and numbered opaque study envelope. The pharmacy staff will send the assigned treatment, which will be administered by the bedside nurse. The vials containing the treatment will be indistinguishable as both furosemide and normal saline placebo are clear, colorless solutions. Thus, the provider, nurse, and patient will be blinded to the treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: October 25, 2020
• First Posted: November 4, 2020
• Study Start: January 4, 2021
• Primary Completion: April 22, 2022
• Study Completion: April 29, 2022
• Last Updated: April 18, 2024
• Results First Posted: April 18, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: Beginning 9 months and ending 36 months following any publication.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

US (1)