Factors Associated With Blood Pressure Control Failure to Intravenous Labetalol in Severe Preeclampsia (RELAPSE)

Assessment of the Association Between Predefined Factors and Response or Failure of Blood Pressure Control With Intravenous Labetalol Monotherapy in Severe Preeclampsia: a Multicenter Observational Study

Severe preeclampsia is a serious pregnancy complication that can lead to severe maternal and fetal outcomes, particularly when blood pressure is not adequately controlled. In France, intravenous labetalol is recommended as the first-line treatment for severe hypertension in preeclampsia. However, in clinical practice, failure to control blood pressure with labetalol is frequently observed, and the factors associated with this lack of response remain poorly understood.

The RELAPSE study is a prospective, multicenter observational study designed to identify factors associated with failure of blood pressure control with intravenous labetalol monotherapy in patients with severe preeclampsia.

The main hypothesis is that certain patient characteristics, such as maternal clinical profile, obstetric history, or biological parameters, may be associated with a higher risk of treatment failure. Identifying these factors could help clinicians better anticipate inadequate response to labetalol and adapt treatment strategies more rapidly.

Data will be collected from routine clinical care without modifying patient management. Patients will be followed from the initiation of intravenous labetalol until hospital discharge. The study will include approximately 350 patients across multiple centers.

By improving the understanding of predictors of treatment failure, this study aims to contribute to better management of severe preeclampsia and to reduce maternal and neonatal complications.

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Preeclampsia

Detailed Description

Severe preeclampsia is a serious pregnancy complication associated with maternal and fetal morbidity and mortality, mainly due to insufficient blood pressure control. Intravenous labetalol is recommended as first-line treatment, but treatment failure is frequently observed in clinical practice, and its predictors are not well established.

The RELAPSE study is a prospective, multicenter observational study aiming to assess the association between predefined patient characteristics and failure of blood pressure control with intravenous labetalol monotherapy.

Data will be collected prospectively from routine clinical care and recorded in an electronic case report form. No additional procedures will be performed, and patient management will not be modified.

Approximately 350 patients will be included across multiple centers. Participants will be followed from initiation of intravenous labetalol until hospital discharge (up to a maximum of 7 days).

The primary analysis will evaluate the association between treatment failure and predefined factors using multivariable logistic regression. Results will be expressed as odds ratios with 95% confidence intervals.

This study aims to improve the identification of patients at risk of treatment failure and contribute to better management of severe preeclampsia.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

• Study Contact: Name: Agnès LE GOUEZ-DIVISIA; Phone Number: +33 1 45 37 42 73; Email: agnes.le-gouez@aphp.fr

Study Locations

• France
  • Bordeaux, France
    • CHU Bordeaux
    • Contact: Aurélie SAN MIGUEL
  • Clamart, France
    • Hôpital Antoine Béclère
    • Contact: Agnès LE GOUEZ-DIVISIA; Phone Number: +33 1 45 37 42 73; Email: agnes.le-gouez@aphp.fr
  • Clermont-Ferrand, France
    • CHU Clermont-Ferrand
    • Contact: Martine BONNIN; Email: mbonnin@chu-clermontferrand.fr
  • Le Kremlin-Bicêtre, France
    • Hopital Bicetre
    • Contact: Marie BRUYERE; Phone Number: +33 1 45 21 34 41; Email: marie.bruyere@aphp.fr
  • Lille, France
    • CHU Lille
    • Contact: Max GONZALEZ-ESTEVEZ; Email: max.gonzalezestevez@chu-lille.fr
  • Lyon, France
    • CHU Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant
    • Contact: Lionel BOUVET
  • Martigues, France
    • CHU Martinique
    • Contact: Thibaut RACKELBOOM; Email: thibaut.rackelboom@chu-martinique.fr
  • Nancy, France
    • CHRU Nancy
    • Contact: Florence VIAL; Email: F.VIAL@chru-nancy.fr
  • Nérac, France
    • CH Agen-Nérac
    • Contact: Sandrine PAQUIN
  • Nîmes, France
    • CHU Caremeau
    • Contact: Estelle MORAU
  • Paris, France
    • Hopital Necker
    • Contact: Hawa KEITA-MEYER; Phone Number: +33 1 44 49 41 72; Email: hawa.keita@aphp.fr
  • Paris, France
    • Hôpital Cochin Port Royal
    • Contact: Catherine FISCHER; Phone Number: +33 1 58 41 41 41; Email: catherine.fischer2@aphp.fr
  • Paris, France
    • Hôpital Armand-Trousseau
    • Contact: Marie-Pierre BONNET; Phone Number: +33 1 44 73 61 99; Email: marie-pierre.bonnet@aphp.fr
  • Roubaix, France
    • CH de Roubaix
    • Contact: Anne-Sophie BAPTISTE; Email: anne-sophie.baptiste@ch-roubaix.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult pregnant women with severe preeclampsia requiring intravenous labetalol as part of routine clinical care.

Description

Inclusion Criteria:

• Adult patient (age ≥ 18 years)
• Pregnancy ≥ 24 weeks of gestation with one or more viable fetuses and severe preeclampsia requiring intravenous labetalol administration, either as continuous infusion (IVSE) or intravenous bolus titration

Exclusion Criteria:

• Contraindication to labetalol (asthma, chronic obstructive pulmonary disease, bradycardia, current or history of intracardiac conduction disorders, or history of hypersensitivity reaction)
• Intravenous antihypertensive treatment initiated prior to inclusion
• Patient refusal or objection to the use of her healthcare data for research purposes

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure of blood pressure control with intravenous labetalol monotherapy	Composite outcome defined as failure to achieve blood pressure control with intravenous labetalol monotherapy in patients with severe preeclampsia. Failure is defined by the occurrence of at least one of the following: addition or switch to another antihypertensive treatment; persistence of severe hypertension after four intravenous labetalol boluses; persistence of hypertension despite continuous intravenous labetalol infusion at the maximum dose of 1 mg/kg/h; or occurrence of a complication attributable to inadequate blood pressure control (e.g., stroke, eclampsia, pulmonary edema, maternal or neonatal death).	During the first hour following initiation of intravenous labetalol administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects related to intravenous labetalol	Occurrence of adverse events potentially related to labetalol administration, including allergic reactions, bronchospasm, and neonatal hypoglycemia.	During the first hour following initiation of intravenous labetalol administration
Safety of intravenous labetalol administration	Occurrence of safety events defined as maternal hypotension (systolic blood pressure < 90 mmHg, diastolic blood pressure < 60 mmHg, or mean arterial pressure < 65 mmHg) and/or maternal bradycardia (heart rate < 50 beats per minute).	During the first hour following initiation of intravenous labetalol administration
Maternal and fetal morbidity and mortality	Occurrence of maternal and fetal complications related to severe preeclampsia or inadequate blood pressure control, including stroke, eclampsia, intracranial hemorrhage, placental abruption, intrauterine fetal death, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, pulmonary edema, maternal death, or neonatal death.	From initiation of intravenous labetalol treatment until hospital discharge (up to 7 days)
Predictive dose of intravenous labetalol failure	Total dose of intravenous labetalol administered prior to meeting criteria for treatment failure.	From initiation of intravenous labetalol treatment until treatment failure or blood pressure control, assessed during hospitalization (up to 7 days)
Emergency cesarean delivery	Occurrence of emergency cesarean section during hospitalization.	From initiation of intravenous labetalol treatment until hospital discharge (up to 7 days)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): May 7, 2026
• Study Completion (Estimated): May 7, 2026

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Severe preeclampsia; maternal morbidity; hypertensive disorders of pregnancy; pregnancy-related hypertension; antihypertensive treatment fa; intravenous labetalol; blood pressure control
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension, Pregnancy-Induced; Pre-Eclampsia
• Other Study ID Numbers: APHP251576

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No