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…
ID
Source
Brief title
Condition
- Maternal complications of pregnancy
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
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.
Background summary
Nicardipine is a very effective treatment for severe hypertension in pregnancy
and is increasingly considered as first line treatment option in many obstetric
wards in the Netherlands. No maternal pharmacokinetic and pharmacodynamic data
are available, which are necessary for the development of an optimal dosage
schedule and for safety aspects of the mother, the fetus and neonate. This is a
field that needs to be explored.
Study 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.
Study design
prospective observational study.
Study burden and risks
Since many years nicardipine is the option of 1st choice (in the Isala Clinics
and Erasmus University Hospital Rotterdam) for treatment of severe hypertension
in pregnancy. Nicardipine showed to be very effective and no severe maternal or
fetal complications due to continuous treatment with nicardipine occurred (data
being analysed). Review of the literature on this subject shows significant
decrease in systolic and diastolic blood pressure in all patients with no
severe maternal or fetal complications. Still only limited data are available
of intravenous use of nicardipine for treatment of severe hypertension in
pregnancy, and further research is needed to provide the best dose response
ratio for nicardipine used for treatment of severe hypertension in pregnancy.
Risk of study participation is negligible. All patients receive nicardipine
treatment as part of standard clinical care. Blood samples (1mL) will be taken
from an intra-arterial catheter. Blood pressure in the patients is and will be
monitored via an intra-arterial catheter, which avoids repetitive venous
bloodsampling. Other haemodynamic parameters will be determined using
non-invasive arterial pressure waveform analysis (Finapres®).
Dr Molewaterplein 60
Rotterdam 30154 GJ
NL
Dr Molewaterplein 60
Rotterdam 30154 GJ
NL
Listed location countries
Age
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
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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-005330-10-NL |
| CCMO | NL42054.075.12 |