Randomized Controlled Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients.

NCT02050529 | Completed Phase 2 DMC

• 1 other identifier: Labetalol in Severe preg HTN
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

Severe Hypertension in pregnancy demands urgent treatment because of high mortality \& morbidity in obstetric patients. Hydralazine, the most commonly used agent, causes sudden hypo tension and tachycardia. Labetalol because of combined α and β blocking effects lacks these side effects. Most recent Cochrane systematic review on use of anti hypertensive drugs in pregnancy related hypertension, could include only four trials of comparison of Hydralazine with Labetalol. Three out of total 4, had sample size ranging from 20-60 obstetric, with total sample size ranging from 19-30. Only 2 trials reported severe persistent hypertension.This review could not conclude about comparative effects due to insufficient data and suggested that further trials should compare Hydralazine with Nifedipine or labetalol, and to report severe persistent hypertension and adverse feto-maternal effects. OBJECTIVES:1) To compare efficacy and severe persistent hypertension after intravenous Labetalol versus Hydralazine, within maximum 5 drug boluses, in obstetric severe hypertensive patients at Civil Hospital Karachi. 2\) To compare immediate adverse maternal and fetal effects in the study group. 3) Furthermore, to assess response to treatment, in terms of patient and disease characteristics. STUDY DESIGN: Randomized controlled trial. SETTING \& DURATION OF STUDY: Gynaecology Unit I, Civil hospital Karachi, from Oct 2012 to Sep 2014 METHODS: Total one hundred eighty-four patients with, severe hypertension (systolic blood pressure(S.B.P)≥160 and/or diastolic blood pressure(D.B.P) ≥110 mm Hg) at greater than 28 weeks of pregnancy or upto 72 hours after delivery, were enrolled and randomly allocated to drug A or B. At enrollment, 94 patients were allocated to Labetalol to 96 to Hydralazine through simple randomization. Since six cases were excluded due to insufficient information( 2 from group A and 4 from group B) so finally data of 92 patients in each group was analyzed. Primary outcome measures were lowering of S.B.P to \<160 mm Hg and D.B.P \<110 mm Hg (efficacy)and severe persistent hypertension. In addition maternal hypo tension, tachycardia, bradycardia, adverse effect on fetal heart, still birth and neonatal bradycardia were measured. EXPECTED OUTCOME: Efficacy, severe persistent hypertension and side effects of Labetalol versus Hydralazine, in our population were determined. Assessment of response to Drug A and B, will help in choosing a drug for different patient and disease characteristics.

Conditions

Hypertension, Pregnancy Induced; Hydralazine Adverse Reaction; Pre-eclampsia; Pre-eclampsia Superimposed Pre-existing Hypertension

Keywords

Hypertension, Pregnancy induced; Pre-eclampsia; Eclampsia; Labetalol; Hydralazine

Outcome Measures

Primary Outcomes (1)

• Efficacy (Reduction in blood pressure below thresholds).

  Reduction in thresholds for severe hypertension in obstetric patients i.e systolic blood pressure \<160 mm Hg systolic and \<110 mm Hg diastolic blood pressure, with allocated drug treatment protocol and specified bolus dosages in the intervention and control(Active comparator) arms.

  From 10 minutes upto maximum of 50 minutes from the start of Labetalol treatment (intervention arm A) and from 20 minutes up to maximum 100 minutes after start of Hydralazine treatment(control arm; B)

Secondary Outcomes (5)

• Maternal tachycardia

  Within 120 minutes of administration of any allocated drug bolus.

• Bradycardia

  Upto 120 minutes of last intravenous drug bolus administration in both arms

• Bronchospasm

  Upto 120 minutes of administration of any intravenous drug bolus.

• Maternal hypotension

  Within 120 minutes of administration of allocated drug bolus in each arm.

• Adverse effect on fetal heart

  2 hours after starting treatment

Study Arms (2)

Labetalol

EXPERIMENTAL

This group (Group A; Labetalol) receiveD intravenous(IV) labetalol manufactured by Zafa pharmaceutical, 50mg/10 ml ampoule) bolus doses administered over 2 minutes, at 10 minutes interval. Initially dose of 20 mg wAS administered, and if required repeated in increments of 40 mg,80 mg,80 mg,80 mg every 10 minutes till SBP became \<160 and DBP \<110 mm Hg, upto a maximum cululative dose of 300mg(total 5 bolus doses).During this time pulse and blood pressure were checked every 10 minutes.

Drug: Labetalol

Hydralazine

ACTIVE COMPARATOR

This group (Hydralazine;Group B) received intravenous Hydralazine and served control. Bolus doses of 5 mg administered over 2 minutes, at 20 minutes interval. Pulse and blood pressure were checked every 10 minutes interval. If SBP threshold of 160 mm Hg or DBP 110 mm Hg was still reached after 20 minutes, then second bolus was repeated. Similarly if after 20 minutes SBP was still ≥160 or DBP ≥110 mm Hg, then third dose was given. If SBP or DBP thresholds were still exceeded after 20 minutes then similarly 4th and 5th dose of 5 mg were given. Failure to reduce SBP\<160 or DBP\<110 after consecutive maximum 5 boluses(total 25 mg) was labeled as severe persistent hypertension.

Drug: Hydralazine

Interventions

Labetalol DRUG

Group A( Labetalol) will be receive intravenous labetalol bolus doses as specified in protocol summary.

Also known as: Trandate

Labetalol

Hydralazine DRUG

Group B(Hydralazine) will serve as control and will receive active comparator Hydralazine intravenous bolus doses as specified in summary.

Also known as: Apresoline

Hydralazine

Eligibility Criteria

• Age: 15 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Pregnancy greater than 28 wks(gestational age determined by ultrasound prior to 20 weeks which if unavailable then by uterine size at first prenatal visit or by last menstrual period) with gestational hypertension, severe preeclampsia, chronic hypertension, chronic hypertension with superimposed preeclampsia, eclampsia and unclassified hypertension.
• Postpartum patients, upto 72 hours after delivery, diagnosed as gestational hypertension, severe preeclampsia, chronic hypertension, chronic hypertension with superimposed preeclampsia, eclampsia and unclassified hypertension.
• Patients with singleton or multiple pregnancy.
• Patients of all ages and parity.

You may not qualify if:

• Patients with asthma.
• Patients with cardiac failure and heart block.
• Patients with pacing device in place or any type of cardiac arrhythmia. -

Sponsors & Collaborators

• Dow University of Health Sciences: lead

Study Sites (1)

Civil Hospital Karachi

Karachi, Sindh, 74200, Pakistan

Location

MeSH Terms

Conditions

Hypertension, Pregnancy-Induced; Pre-Eclampsia; Eclampsia

Interventions

Labetalol; Hydralazine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Salicylamides; Amides; Amines; Phthalazines; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Saima A Siddiqui, MCPS,FCPS

  Dow University of Health Science Karachi

  PRINCIPAL INVESTIGATOR

• Nazeer Khan, PhD

  Dow University of Health Health Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 29, 2014
• First Posted: January 30, 2014
• Study Start: October 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: March 1, 2015
• Last Updated: October 26, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)