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

This study is currently recruiting participants.
Verified January 2014 by Dow University of Health Sciences
Sponsor:
Information provided by (Responsible Party):
Saima Aziz Siddiqui, Dow University of Health Sciences
ClinicalTrials.gov Identifier:
NCT02050529
First received: January 29, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

Severe Hypertension in pregnancy demands urgent treatment because of high mortality & morbidity in obstetric patients. Hydralazine, the most commonly used agent, causes sudden hypotension and tachycardia. Labetalol because of combined α and β blocking effects lacks these side effects. Cochrane systematic review could include only three trials of comparison of hydralazine with labetalol. All three had sample size ranging from 20-60 obstetric, including 19-30 pregnant women. 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 of labetalol versus hydralazine for control of pregnancy related severe hypertension.2) To compare adverse maternal and fetal effects of the two drugs.

3) Furthermore, to develop risk assessment model for 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 over a period of 1 year.

METHODS: Total one hundred eighty patients with, severe hypertension(systolic blood pressure(SBP)≥160 and/or diastolic blood pressure(DBP) ≥110 mm Hg) at greater than 28 weeks of pregnancy or upto72 hours after delivery, will be enrolled. In each group 90 patients will be allocated to intravenous labetalol or hydralazine using simple random sampling. Primary outcome measures will be lowering of SBP to <160 mm Hg and DBP <110 mm Hg and severe persistent hypertension. In addition maternal hypotension, tachycardia, bradycardia, adverse effect on fetal heart, still birth and neonatal bradycardia will be measured.

EXPECTED OUTCOME: Efficacy and side effects of labetalol against hydralazine, in our population will be determined. Assessment model for response to treatment, will help in choosing a drug with better efficacy and minimal side effect profile for different patient and disease profiles.


Condition Intervention Phase
Hypertension, Pregnancy Induced
Hydralazine Adverse Reaction
Pre-eclampsia
Pre-eclampsia Superimposed Pre-existing Hypertension
Drug: Labetalol
Drug: Hydralazine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Clinical Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients at a Tertiary Care Hospital of Karachi.

Resource links provided by NLM:


Further study details as provided by Dow University of Health Sciences:

Primary Outcome Measures:
  • Sever persistent hypertension [ Time Frame: After the time period of maximum number of drug boluses, i.e 50 minutes after beginning administration of labetalol( maximum 5 boluses) and 80 minutes after hydralazine (maximum 4 boluses every 20 minutes interval) ] [ Designated as safety issue: No ]
    Systolic blood pressure ≥160 or DBP≥ 110 mm of Hg after the administration of consecutive maximum doses of allocated drug treatment i.e 5 incremental doses of labetalol(20 mg,40,80,80,80) and 4 doses of Hydralazine 5 mg doses in respective study arms.

  • Efficacy (Reduction in blood pressure below thresholds). [ Time Frame: Upto 50 minutes of start of labetalol treatment(intervention arm) and 80 minutes after start of hydralazine treatment(control arm; B) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Maternal tachycardia [ Time Frame: Within 120 minutes of administration of any allocated drug bolus. ] [ Designated as safety issue: Yes ]
    Maternal tachycardia will be defined as maternal heart rate =>100 beats/min developing within 120 minutes of administration of any allocated drug bolus. After the beginning of therapy heart rate will be monitored every 10 minutes during administration of drug boluses and every15 minutes within first 2 hours of last intravenous bolus of drug in both arms.

  • Bradycardia [ Time Frame: Upto 120 minutes of last intravenous drug bolus administration in both arms ] [ Designated as safety issue: Yes ]
    Maternal bradycardia defined as heart rate <60 beats/min developing within 120 minutes of administration of last assigned drug bolus. After the begining of therapy heart rate will be monitored every 10 minutes during administration of drug boluses and every15 minutes within first 2 hours of last intravenous bolus of drug in both arms.

  • Bronchospasm [ Time Frame: Upto 120 minutes of administration of any intravenous drug bolus. ] [ Designated as safety issue: Yes ]
    Rhonchi developing on ausculation of chest when there was absence of Rhonchi before drug administration.

  • Maternal hypotension [ Time Frame: Within 120 minutes of administration of allocated drug bolus in each arm. ] [ Designated as safety issue: Yes ]
    Maternal hypotension will be defined as systolic blood pressure <90 mm Hg and diastolic blood pressure < 60 mm Hg. Blood pressure will be monitored during and after administartion of drug boluses in both the study arms as outlined in summary. Hypotension developing within 120 minutes of administration of drug bolus in both arms will be recorded.


Estimated Enrollment: 180
Study Start Date: February 2013
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Labetalol
This group (Group A; Labetalol) will receive intravenous(IV) labetalol manufactured by Zafa pharmaceutical, 50mg/10 ml ampoule) bolus doses administered over 2 minutes, at 10 minutes interval. Initially dose of 20mg will be administered, and if required repeated in increments of 40 mg,80 mg,80mg,80mg every 10 minutes till SBP becomes <160 and DBP <110 mm Hg, upto a maximum total dose of 300mg(total 5 bolus doses).During this time pulse and blood pressure will be checked every 10 minutes.
Drug: Labetalol
Group A( Labetalol) will be receive intravenous labetalol bolus doses as specified in protocol summary.
Other Names:
  • Labetalol
  • Trandate
Active Comparator: Hydralazine
This group (Hydralazine;Group B) will receive intravenous Hydralazine and will serve as control. Bolus doses of 5 mg administered over 2 minutes, at 20 minutes interval. Pulse and blood pressure will be checked every 10 minutes interval. If SBP threshold of 160 mm Hg or DBP 110 mm Hg is still reached after 20 minutes, then second bolus will be repeated. Similarly if after 20 minutes SBP is still ≥160 or DBP ≥110 mm Hg, then third dose will be given. If SBP or DBP thresholds are still exceeded after 20 minutes then similarly 4th dose of 5 mg will be given. Failure to reduce SBP<160 or DBP<110 after consecutive maximum 4 boluses(total 20 mg) will be labeled as severe persistent hypertension.
Drug: Hydralazine
Group B(Hydralazine) will serve as control and will receive active comparator Hydralazine intravenous bolus doses as specified in summary.
Other Names:
  • Hydralazine
  • Apresoline

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 49 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

INCLUSIONS CRITERIA Pregnant or post partum patients with systolic blood pressure ≥160mm of Hg or diastolic BP ≥110 mm Hg, on repeat measurement of blood pressure after 15 minutes of rest, meeting following inclusion criteria will be included.

  1. 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.
  2. Postpartum patients, upto 72 hours after delivery, diagnosed as gestational hypertension, severe preeclampsia, chronic hypertension, chronic hypertension with superimposed preeclampsia, eclampsia and unclassified hypertension.
  3. Patients with singleton or multiple pregnancy.
  4. Patients of all ages and parity.

Exclusion Criteria:

  1. Patients with asthma.
  2. Patients with cardiac failure and heart block.
  3. Patients with pacing device in place or any type of cardiac arrhythmia. -
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02050529

Contacts
Contact: Saima A Siddiqui, MCPS, FCPS +92-3122901203 saima.aziz@duhs.edu.pk

Locations
Pakistan
Civil Hospital Karachi Recruiting
Karachi, Sindh, Pakistan, 74200
Principal Investigator: Saima A Siddiqui, MCPS, FCPS         
Sub-Investigator: Ayesha Khan, FRCOG         
Sub-Investigator: Nazeer Khan, PhD         
Sponsors and Collaborators
Dow University of Health Sciences
Investigators
Principal Investigator: Saima A Siddiqui, MCPS,FCPS Dow University of Health Science Karachi
Study Director: Nazeer Khan, PhD Dow University of Health Health Sciences
  More Information

No publications provided

Responsible Party: Saima Aziz Siddiqui, Assistant Professor, Dow University of Health Sciences
ClinicalTrials.gov Identifier: NCT02050529     History of Changes
Other Study ID Numbers: Labetalol in Severe preg HTN
Study First Received: January 29, 2014
Last Updated: January 29, 2014
Health Authority: Pakistan:" Pakistan Research & Ethics Committee"

Keywords provided by Dow University of Health Sciences:
Hypertension, Pregnancy induced
Pre-eclampsia
Eclampsia
Labetalol
Hydralazine

Additional relevant MeSH terms:
Eclampsia
Hypertension
Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications
Vascular Diseases
Cardiovascular Diseases
Labetalol
Hydralazine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-Antagonists
Vasodilator Agents

ClinicalTrials.gov processed this record on April 17, 2014