Randomized Clinical Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients.
Recruitment status was Recruiting
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.
Hypertension, Pregnancy Induced
Hydralazine Adverse Reaction
Pre-eclampsia Superimposed Pre-existing Hypertension
|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.|
- 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.
- 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.
|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)|
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.
Group A( Labetalol) will be receive intravenous labetalol bolus doses as specified in protocol summary.
Other Name: 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.
Group B(Hydralazine) will serve as control and will receive active comparator Hydralazine intravenous bolus doses as specified in summary.
Other Name: Apresoline
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02050529
|Contact: Saima A Siddiqui, MCPS, FCPSfirstname.lastname@example.org|
|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|
|Principal Investigator:||Saima A Siddiqui, MCPS,FCPS||Dow University of Health Science Karachi|
|Study Director:||Nazeer Khan, PhD||Dow University of Health Health Sciences|