Viewing Study NCT02050529



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Last Modification Date: 2024-10-26 @ 11:18 AM
Study NCT ID: NCT02050529
Status: COMPLETED
Last Update Posted: 2018-10-26
First Post: 2014-01-29

Brief Title: Randomized Controlled Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients
Sponsor: Dow University of Health Sciences
Organization: Dow University of Health Sciences

Study Overview

Official Title: Randomized Controlled Trial of Labetalol Versus Hydralazine for Severe Hypertension in Obstetric Patients at a Tertiary Care Hospital of Karachi
Status: COMPLETED
Status Verified Date: 2018-10
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
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 hypertensionThis 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

OBJECTIVES1 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 pressureSBP160 andor diastolic blood pressureDBP 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 SBP to 160 mm Hg and DBP 110 mm Hg efficacyand 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
Detailed Description: Study HypothesisStudy hypothesis is that

1 There is no difference in efficacy and severe persistent hypertension after intravenous Labetalol versus Hydralazine
2 There is no difference in adverse maternal and fetal effects

Patients diagnosed to have severe hypertensionon 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 11 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 mg80 mg and again 80 mg repeated twice more total 5 doses maximum cumulative dose 300 mg till primary end point ie Systolic blood pressure 160 mm Hg and diastolic blood pressure 110 mm Hg was reached

BHYDRALAZINE First dose of 5 mg slow intravenously over 2 minutes if required followed at 20 minutes intervals by subsequent doses of 5 mg repeated upto a maximum of 4 more times total 5 doses maximum cumulative dose 25 mg till primary end point ie Systolic blood pressure 160 mm Hg and diastolic blood pressure 110 mm Hg was reached

Group A received intravenousIV Labetalol 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 mg80 mg 80 mg 80 mg every 10 minutes till SBP was reduced 160 and DBP 110 mm Hg upto a maximum cumulative dose of 300 mgtotal 5 bolus dosesDuring this time pulse and blood pressure were checked every 10 minutes Failure to reduce SBP160 or DBP110 with consecutive maximum 5 boluses 300mg was labelled severe persistent hypertensionIn such case patient was switched to cross over treatment with hydralazine according to dosing schedule for group B and consultation with critical care teamMedical cardiovascular critical care specialist was sought Blood pressure and pulse were recorded at 10 minutes interval till blood pressure was reduced below threshold levels SBP160 and diastolic 110 mm of HgOnce this level was achieved then monitoring was continued every 15 minutes interval for two hours every 30 minutes interval for 1 hour and thereafter at hourly interval for next 4 hours

Group B control received intravenous Hydralazine 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 of 160 mm Hg or DBP 110 mm Hg 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 5 th dose of 5 mg were given Failure to reduce SBP160 or DBP110 after consecutive maximum 5 bolusestotal 25 mg was labeled as severe persistent hypertensionOnce blood pressure was reduced below threshold level pulse and blood pressure were monitored similar to group A Labetalol Failure to reduce SBP160 or DBP110 after consecutive maximum 5 bolusestotal 25 mg was labelled as severe persistent hypertension which was considered as treatment failure In such case patient was switched to cross over treatment with Labetalol according to dosing schedule for group A and emergency consultation with critical care team Medical cardiovascular critical care specialist was soughtPulse and blood pressure was rechecked every 10 minutes till SBP was reduced 160 mm Hg and DBP 110 mm of Hg and thereafter as stated for group A

Our use of alternate treatment for severe persistent hypertension in both groups is keeping in line with the most recent American College of Obstetricians and Gynaecologists committee opinion 2015 recommendation

Critical care team had authority to intervene at anytime if they thought it was necessary to interrupt treatment protocol due to patient condition or in case of non response to cross over drug

Cardiotocography CTG was done in pregnant women on admission and it was repeated 2 hour after initiation of therapy

Primary outcome measures will be lowering of SBP160 mm Hg and DBP 110 mm Hg in scheduled dosages of allocated treatmentprimary end point of study and severe persistent hypertension ie treatment failure

Secondary outcome measures were adverse drug effects ie maternal hypotension tachycardia bradycardia palpitation headache nausea vomiting dizziness bronchospasm oliguria adverse effect on fetal heart and neonatal bradycardia

In both study arms patients monitoring and decisions for delivery of pregnant patients were taken according to department protocol which is consistent with standard recommendations

OPERATIONAL DEFINITIONS

1 Gestational hypertension was diagnosed with a BP of 14090 mm Hg after 20 weeks of pregnancy in previously normotensive women proven by antenatal record

2 Preeclampsia was defined as BP 14090 mm Hg along with proteinuria 1 on dipsticks in a previously normotensive non-proteinuric woman proven by antenatal record

3 Chronic Hypertension was diagnosed by history of preexisting hypertension or by detecting persistent elevation of BP14090 mm Hg prior to 20 weeks of pregnancy

4 Severe preeclampsia was defined as BP 160110 along with proteinuria1 on dipstick with or without one or more of the following features ie headache visual disturbance upper right quadrantepigastric pain pulmonary oedema elevated alanine aminotransferase ALT raised creatinine hemolysis thrombocytopenia intrauterine growth restrictionIUGR in a previously normotensive non proteinuric woman proven by antenatal record

5 Eclampsia was diagnosed by generalized tonic clonic seizures in woman with hypertensive disorder not attributable to any other cause

6 Efficacy was defined as lowering of systolic BP to 160mm Hg and diastolic BP110 mm Hg

7 Severe persistent hypertension was defined by SBP 160 or DBP 110 mm of Hg after the administration of consecutive maximum 5doses of allocated drug treatment

8 Maternal hypotension was defined as systolic BP 90 mm Hg or diastolic BP60 mm Hg

9Maternal tachycardia was defined as heart rate 100 bm in the absence of fever cardiovascular disease

10Normal CardiotocographCTG was defined as having following 4 features i Baseline heart rate 110-160 beatsminute ii Variability5-25 beatsminutes iii ateast 2 accelerations of 15 bm lasting for15 seconds iv No decelerations

11Adverse effect on fetal heart rate FHR was defined as ipresence of any type of deceleration without uterine contraction iiReduced variability5 bm for 40 minutes iii Variable late decelerations in the presence of uterine contractions iii FHR110 bm or 160 bm detected on CTG 2 hour after starting treatment with a baseline normal CTG on admission

12Placental abruption was defined as clinical features of uterine tenderness with evidence of retroplacental clot at delivery

13 Oliguria was defined as urinary output30 mlhr for 4 hours 14 Neonatal bradycardia will be defined as heart rate100 bm DATA ANALYSIS Data was entered and analyzed through Statistical package for Social Sciences Software SPSS version 20 Continuous variables ie age parity gestation Systolic blood pressure SBPDiastolic blood pressure DBP Mean arterial pressure MAP at randomization are presented as mean SD whereas mean reduction in MAP number of boluses of antihypertensive time to achieve blood pressure control and mean dose to achieve desired level of control were analyzed by students t test or Mann Whitney U test according to normality distribution Qualitative variables ie severe persistent hypertension maternal hypotension tachycardia bradycardia headache palpitation nausea vomitingdizziness oliguria placental abruption adverse effects on fetal heart rate still birth neonatal bradycardia cesarean section Apgar score 7 at 1 and 5 minutes and neonatal intensive care admission were analyzed by chi square and Fischers exact testwhere applicable For analyzing adverse effect on FHR patients with admission CTG showing fetal bradycardia 110 bm tachycardia 160 bm variability 5 bm for 40 minutes variable and late decelerations were excluded Adverse effect on FHR was studied on all 169antenatal women and neonatal outcomes Apgar neonatal bradycardia was studied on patients delivering within 24 hours of enrollment

Furthermore regression model based on predictors of age cut offs 35 years weight 70 kg and gestation 34 weeks was also done for both drugs

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: None
Is a FDA Regulated Device?: None
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None