Randomized Controlled Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients.
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|ClinicalTrials.gov Identifier: NCT02050529|
Recruitment Status : Completed
First Posted : January 30, 2014
Last Update Posted : October 26, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Hypertension, Pregnancy Induced Hydralazine Adverse Reaction Pre-eclampsia Pre-eclampsia Superimposed Pre-existing Hypertension||Drug: Labetalol Drug: Hydralazine||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||190 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Randomized Controlled Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients at a Tertiary Care Hospital of Karachi.|
|Actual Study Start Date :||October 2012|
|Actual Primary Completion Date :||September 2014|
|Actual Study Completion Date :||March 2015|
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.
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) 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.
Group B(Hydralazine) will serve as control and will receive active comparator Hydralazine intravenous bolus doses as specified in summary.
Other Name: Apresoline
- Efficacy (Reduction in blood pressure below thresholds). [ Time Frame: 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) ]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. ]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 ]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. ]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. ]Systolic blood pressure <90 mm Hg and diastolic blood pressure < 60 mm Hg.
- Adverse effect on fetal heart [ Time Frame: 2 hours after starting treatment ]
Any of the following features on cardiotocograph (C.T.G) trace, 2 hour after starting treatment, with a normal baseline C.T.G on admission.
i) Presence of any type of deceleration without uterine contractions ii) Reduced variability<5 b/m for >40 minutes, iii) Persistent variable and late decelerations iii) Baseline fetal heart rate (F.H.R)<110b/m or >160b/m any of the following features on cardiotocography (CTG) tracing, 2 hour after starting treatment, with a normal CTG on admission. ,30, 31 i) Presence of any type of deceleration without uterine contractions ii) Reduced variability<5 b/m for >40 minutes, iii) Persistent variable and late decelerations iii) Baseline fetal heart rate (F.H.R)<110b/m or >160b/m was defined by any of the following features on cardiotocography (CTG) tracing, 2 hour after starting treatment, with a normal CTG on admission. ,30, 31 i) Presence of any type of deceleration without uterine contractions ii) Reduced variability<5 b/m for >40 minu
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02050529
|Civil Hospital Karachi|
|Karachi, Sindh, Pakistan, 74200|
|Principal Investigator:||Saima A Siddiqui, MCPS,FCPS||Dow University of Health Science Karachi|
|Study Director:||Nazeer Khan, PhD||Dow University of Health Health Sciences|