Pregnant patients with preeclampsia (hypertension and protein/creatinine ratio = 30mg/mmol or = 300mg protein/24hours) complicated with severe hypertension (systolic bloodpressure = 160mmHg and/or diastolic blood pressure = 110mmHg). Gestational age = 20 weeks
Conditions
Interventions
Trade Name: Cardene IV
Product Name: nicardipine
Product Code: RVG 14835
Pharmaceutical Form: Concentrate and diluent for solution for infusion
Sponsors
Erasmus University Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Pregnant patients with preeclampsia (hypertension and protein/creatinine ratio = 30mg/mmol or = 300mg protein/24hours) complicated with severe hypertension (systolic bloodpressure = 160mmHg and/or diastolic blood pressure = 110mmHg) gestational age = 20 weeks working knowledge of Dutch language Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Fetal indication for immediate delivery, ie. signs of fetal distress: spontaneous repeated persistent unprovoked decelerations on CTG Fetal death or major fetal congenital anomalies or estimated fetal weight below 500 grams Placental abruption Concomitant medication: nifedipine, cimetidine, labetalol Clinically relevant pulmonary edema, defined as clinically relevant respiratory failure or severe respiratory distress requiring oxygen supplementation (more than 10 litres), with rales and/or pulse oximetry of <94% on room air Eclampsia Suspicion of (sub)capsular liverhematoma on physical examination Renal failure (creatinine clearance < 40 mL/min) • Suspicion of cerebro-vascular incident on physical examination • Suspicion of trombo-embolism on physical examination • Other severe maternal complications • Maternal age <16 years • Mentally incapacitated patient • Impossible to place an intra-arterial catheter.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Our aim is to determine a Pharmacokinetic/Pharmacodynamic (PkPd) based dosing model for nicardipine used for treatment of severe hypertension in preeclamptic patients. The model is based upon determination of maternal, fetal and neonatal plasma levels of nicardipine, and the corresponding changes in maternal haemodynamic parameters after administration of nicardipine.;Secondary Objective: not applicable;Primary end point(s): Maternal first half life (1st 24 hours after initiation), second half life (24hours after administration), distribution half time, elimination half time, assessing risk of accumulation. Changes in blood pressure, heart rate, cardiac output, cardiac index, stroke volume, peripheral resistance, and NT-proBNP values after administration of nicardipine. ;Timepoint(s) of evaluation of this end point: A blank blood sample will be obtained before the start of nicardipine infusion and just before each dosage change. After initiation of nicardipine therapy and following each dosage change 1 ml blood will be drawn at 15 min, 30 min, 1 hour and 2 hours. After target blood pressure is reached 1mL blood will be withdrawn every 6 hours from the arterial catheter until 48 hours after each dosage adjustment or until the end of infusion.One mL blood will be sampled 1, 2, 4, 8, 12, 24 and 48 hours after termination of nicardipine infusion. Just before delivery 1mL blood will be withdrawn. Haemodynamic monitoring is continuous. NT-proBNP will be taken before initiation, during steady state, before delivery, post delivery and 6 months post partum. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Determine concentration gradient to breastmilk. Determine pharmacokinetic parameters in the neonate and if appropriate correlate neonatal pharmacokinetic parameters to neonatal pharmacodynamic changes. Exploring haemodynamic changes in preeclamptic patients with severe hypertension and exploring the haemodynamic transfer to normal in the puerperium.;Timepoint(s) of evaluation of this end point: After delivery breast milk is collected with a maximum of one sample per day with a maximum period of 72 hours. After cord clamping both arterial and venous cord samples (1mL) are taken. A maximum of 3% of the total neonatal circulating volume will be used for this research with blood samples equally distributed in the sample period. The maximum period of neonatal blood sampling is 72 hours. In this period 3 to maximal 6 samples will be taken depending on the weight of the neonate. Haemodynamic parameters will be taken 3 and 6 months post delivery and single measurements will be done in the control group A blood sample for measurement of NT-proBNP will be taken 3 and 6 months post partum and in the control group. | — |
Countries
Netherlands
Contacts
Public ContactS.W.A. Nij Bijvank
Erasmus University Medical Centre
Outcome results
None listed