Randomized Controlled Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients at a Tertiary Care Hospital of Karachi.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 190
- 试验地点
- 1
- 主要终点
- Efficacy (Reduction in blood pressure below thresholds).
研究概览
简要总结
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.
- 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.
详细描述
Study Hypothesis:Study hypothesis is that
- There is no difference in efficacy and severe persistent hypertension after intravenous Labetalol versus Hydralazine.
- There is no difference in adverse maternal and fetal effects.
Patients diagnosed to have severe hypertension(on repeat measurement of BP after 15 minutes of rest), admitted in 24 hour period of emergency, meeting inclusion criteria, were included. One hundred eighty-four patients were enrolled after informed consent and randomly allocated to each treatment arm by 1:1 randomization through simple random allocation.
All eligible pregnant or post partum women with systolic blood pressure ≥160mm of Hg or diastolic BP ≥110 mm Hg, on repeat measurement after 15 minutes of rest, admitted through emergency and outpatients department, were invited for participation in the study. They were enrolled after informed consent. Drug treatment was assigned using simple random sampling.
DATA COLLECTION INSTRUMENT Data was recorded on a case report form (CRF). DOSING SCHEDULE OF DRUGS A) LABETALOL: First dose of 20 mg slow intravenously over 2 minutes, if required followed at 10 minutes intervals by subsequent doses of 40 mg,80 mg, and again 80 mg repeated twice more (total 5 doses, ,maximum cumulative dose 300 mg) till primary end point i.e Systolic blood pressure <160 mm Hg and diastolic blood pressure 110 mm Hg was reached.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 15 Years 至 49 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •Patients with asthma.
- •Patients with cardiac failure and heart block.
- •Patients with pacing device in place or any type of cardiac arrhythmia. -
研究组 & 干预措施
Labetalol
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.
干预措施: Labetalol (Drug)
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.
干预措施: Hydralazine (Drug)
结局指标
主要结局
Efficacy (Reduction in blood pressure below thresholds).
时间窗: 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.
次要结局
- Maternal tachycardia(Within 120 minutes of administration of any allocated drug bolus.)
- Maternal hypotension(Within 120 minutes of administration of allocated drug bolus in each arm.)
- Bronchospasm(Upto 120 minutes of administration of any intravenous drug bolus.)
- Adverse effect on fetal heart(2 hours after starting treatment)
- Bradycardia(Upto 120 minutes of last intravenous drug bolus administration in both arms)
研究者
Saima Aziz Siddiqui
Assistant Professor
Dow University of Health Sciences