Management of Hypertension in the Early Postpartum: a Randomized Controlled Trial

Management of Hypertension in the Early Postpartum Period: Randomized Clinical Trial Comparing Two Antihypertensive Medications

In hypertensive mothers, it is common in clinical practice to substitute methyldopa for another medication, such as captopril, immediately after delivery, which may, as a consequence, cause a rebound effect or an initial lack of blood pressure control until the new medication had a more complete action. Thus, the treatment of hypertension in the puerperium is generally guided by expert opinion and recommendations for guidelines, based on non-robust evidence. OBJECTIVE: To evaluate the control of blood pressure in postpartum women with hypertensive syndromes during pregnancy with the maintenance of the continued use of previously used methyldopa compared to switching from antihypertensive regimen to the use of captopril. METHOD: Randomized, double-blind, drug controlled clinical trial. EXPECTED RESULT: better pressure control with the continued use of methyldopa.

Study Overview

• Status: Completed
• Conditions: Hypertension; Pregnancy-Induced Hypertension in Postpartum; Postpartum Pre-Eclampsia
• Intervention / Treatment: Drug: Methyldopa 250 MG

Detailed Description

Objective: To evaluate blood pressure control during the immediate postpartum in hypertensive women who had used methyldopa during pregnancy, comparing continuation of that drug with switching it for captopril. Methods: A single-blind, randomized clinical trial involving 180 postpartum women with arterial hypertension who had previously used methyldopa during pregnancy at a minimum dose of 750 mg/day for at least one week prior to delivery. Following delivery, the patients were randomized either to continue with methyldopa (minimum dose 250 mg, three times a day) (methyldopa group, n=90) or to switch to captopril (at an initial dose of 25 mg, three times a day) (captopril group, n=90). Logistic regression will be used to compare the groups regarding the potential to maintain blood pressure below 140/90 mmHg at over 50% of measurements postpartum.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Paraíba
    • João Pessoa, Paraíba, Brazil, 58050-585
      • UFPB Paraíba Federal University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• puerpera;
• hypertensive;
• use of methyldopa during pregnancy at a minimum dose of 750 mg / day, for at least 07 days before delivery

Exclusion Criteria:

• Use of other antihypertensive medications or illicit drugs that may interfere with maternal hemodynamics, and / or Contraindications to the use of captopril or methyldopa

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: methyldopa; maintaining postpartum the use of methyldopa 250 mg 01 tablet every 8 hours, being able to double the dose depending on pressure levels, up to 15 days postpartum	Drug: Methyldopa 250 MG; maintaining postpartum the use of methyldopa 250 mg 01 tablet every 8 hours, being able to double the dose depending on pressure levels, up to 15 days postpartum
Active Comparator: captopril; postpartum exchange methyldopa for captopril 25 mg 01 tablet every 8 hours, doubling the dose depending on pressure levels, up to 15 days postpartum	Drug: Methyldopa 250 MG; maintaining postpartum the use of methyldopa 250 mg 01 tablet every 8 hours, being able to double the dose depending on pressure levels, up to 15 days postpartum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Values of blood pressure (systolic blood pressure)	systolic blood pressure values in mmHg (millimeters of mercury) after starting postpartum medication	every 4 hours immediately after the use of medication until hospital discharge
Values of blood pressure (dyastolic blood pressure)	diastolic blood pressure values in mmHg (millimeters of mercury) after starting postpartum medication	every 24 hours immediately after the use of medication until hospital discharge
Values of blood pressure ( mean arterial pressure)	mean blood pressure values in mmHg (millimeters of mercury) after starting postpartum medication	every 4 hours immediately after the use of medication until hospital discharge
Values of heart rate	values of heart rate bpm (beat per minute) after starting postpartum medication	every 4 hours immediately after the use of medication until hospital discharge
Frequency of hypertensive peaks	numbers of hypertensive peaks (Systolic Blood Pressure ≥160 mmHg and / or Diastolic Blood Pressure ≥ 110 mmHg) after starting postpartum medication	every 4 hours immediately after the use of medication until hospital discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of the following laboratory tests ( protein urinary) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the days of puerperium: urinary protein / creatinine (P / C) ratio (measured in mg / dL). Values greater than 300mg/dL of protein in 24h are indicative of pre-eclampsia.	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests ( urea) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: urea ( blood dosage) measure of value ( mg/dL)	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests (creatinine) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: creatinine ( blood dosage) measure of value ( mg/dL)	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests (DHL) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: lactic dehydrogenase -DHL ( blood dosage) measure of value ( UI/L)	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests (uric acid) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: uric acid (blood dosage) measure of value mg/dL	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests aspartate transferase (AST)) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: aspartate transferase (blood dosage) measure of value U/L	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests alanine transferase (ALT) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: alanine transferase (ALT) (blood dosage) measure of value U/L	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests (total bilirubins, direct and indirect ) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: total bilirubins, direct and indirect (blood dosage)- measure of value U/L	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests (platelets) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: platelets/ µL (blood dosage)	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests (glomerular filtration rate) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: calculated by formula Modification of Diet Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI), obtained by the site: http://mdrd.com/	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Profile of the following laboratory tests (sodium, potassium and chlorine) on admission and their evolution during the puerperium	Profile of the following laboratory tests on admission and their evolution during the puerperium: sodium, potassium and chlorine - measure of value (mEq/L)	the first before delivery and the next every 24 hours after delivery until the normalization of the values
Days of hospital stay after delivery until blood pressure control	Days of hospital stay after delivery until blood pressure control (more than 50% of blood pressure measurements less than or equal to 140 x 90 mmHg)	number of days (24 hours) from postpartum hospitalization until normalization of blood pressure
Need for drug use for hypertensive peak ( yes or no)	Clonidine was the drug of choice in the study. The hypertensive peak was considered to be greater than or equal to systolic pressure 160 mmHg and / or diastolic pressure greater than or equal to 110 mmHg.	every 4 hours immediately after the use of medication until hospital discharge
Need to associate another hypotensive drug to control blood pressure ( yes or no)	Need to associate another hypotensive drug to control blood pressure until blood pressure control (more than 50% of blood pressure measurements less than or equal to 140 x 90 mmHg)	immediately after the use of medication until hospital discharge
use of analgesic and anti-inflammatory ( yes or no)	need for analgesic and anti-inflammatory use and the amount used (number of doses)	number of doses in 24 hours for postpartum analgesia
Use of antihypertensive drugs at the time of hospital discharge ( yes or no)	patient was discharged using antihypertensive medication	immediately after discharge from the hospital up to 15 days after delivery
Frequency of adverse effects most often described with medications ( yes or no)	numbers of adverse effects most often described with medications: drowsiness, headache, dizziness, orthostatic hypotension, nausea, vomiting, diarrhea, dry mouth, dry cough, skin rashes, itching, arthralgia, skin lesions, dysgeusia, angioedema	immediately after the use of medication until hospital discharge
maternal complicatios ( yes or no)	maternal complications (eclampsia, HELLP syndrome, impending eclampsia, oliguria, puerperal complications and maternal death) and complications related to hypertensive peaks (stroke, acute myocardial infarction and acute lung edema)	immediately after the use of medication until hospital discharge
satisfactory breastfeeding	satisfactory, unsatisfactory and with difficulty reported by the mother	immediately after the use of medication until hospital discharge
degree of maternal satisfaction with medication	I hated it, I didn't like it, indifferent, I liked it, I loved it (scale of faces)	immediately after the use of medication until hospital discharge
Postpartum depression	Edinburgh Postpartum Depression Scale (EPDS)	immediately after the use of medication until return for evaluation of the patient 15 days after delivery
Neonatal outcomes ( bradycardia) -yes or no	bradycardia( below 100 beats per minute of the newborn)	immediately after the use of medication until hospital discharge
Neonatal outcomes ( hypoglycemia) -yes or no	blood glucose below < 45 mg/dL	immediately after the use of medication until hospital discharge
Neonatal outcomes (Hypothermia) -yes or no	Hypothermia below 36,5 degree celsius	immediately after the use of medication until hospital discharge
Neonatal outcomes (comorbidity) -yes or no	Some unfavorable clinical condition of the newborn (comorbidity)	immediately after the use of medication until hospital discharge
Neonatal outcomes (hypotension) -yes or no	mean arterial pressure (mmHg) below gestational age (weeks)	immediately after the use of medication until hospital discharge

Collaborators and Investigators

• Sponsor: Federal University of Paraíba
• Investigators: Principal Investigator: Andre Telis Araujo, PhD, Federal University of Paraíba; Principal Investigator: Luiz Aparecido Bortolotto, PhD, FMUSP

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Actual): December 16, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: March 31, 2021
• First Submitted That Met QC Criteria: April 5, 2021
• First Posted (Actual): April 8, 2021

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Eclampsia; Pre-Eclampsia; Hypertension, Pregnancy-Induced; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Methyldopa
• Other Study ID Numbers: 19479

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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