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CHIPS trial

Control of Hypertension In Pregnancy Study

Go to the Dutch website. Here you can find:

  - Summary

  - Brochures

  - Sample patient information / informed consent

  - All data forms and Dutch Working Protocol

 

Go to the Canadian website. Here you can find:

  - English protocol

  - Pilot publications

  - Newsletters

  - Information about meetings


Objective
Women with non-severe non-proteinuric pre-existing hypertension (1% of deliveries) or gestational hypertension remote from term (2-3%) represent a high-risk group from both maternal and perinatal perspectives.
It is still unclear how best to manage the non-severe hypertension in order to do more good than harm. The placenta does not autoregulate blood flow, so allowing blood pressure (BP) to be higher may improve uteroplacental perfusion, fetal growth, and ultimately, neonatal well-being. Based on our meta-analyses of RCTs, arguments can be made both for and against ‘less tight’ control of BP (allowing for higher BP levels). ‘Less tight’ control may decrease the risk of small for gestational age (SGA) infants, but may also increase the risk of (transient) severe maternal hypertension, antenatal hospitalisation, and proteinuria at delivery. However, there is insufficient evidence on which to base clinical decisions because of reporting bias and between-trial heterogeneity in outcome. Guidelines are founded mainly on expert opinion. Our national survey found that Canadian obstetricians are divided on these issues. The CIHR-funded CHIPS Pilot Trial confirmed the importance and feasibility of a definitive RCT. Clinicians complied with the interventions and women were satisfied with their care. ‘Less tight’ (vs. ‘tight’) control resulted in higher dBP, and a more favourable effect on perinatal outcomes. We need a definitive RCT.

Study design
International multicentre RCT that will recruit over 4 years.
 
Study population
1,028 women (514/group) from 50 tertiary and community centres.

 

Inclusion criteria

Pre-existing/gestational hypertension

Office dBP 90-105mmHg (or dBP 85-105mmHg if on antihypertensive medication)

Live fetus

Gestational age between 14 and 33+6 weeks

 

Exclusion criteria

Severe systolic hypertension

Proteinuria

Contraindication to either arm of trial or to prolongation of pregnancy

ACE inhibitor use in pregnancy at 14 or more weeks of gestation

Known multiple gestation or lethal/major fetal anomaly

Plan to terminate pregnancy

Prior participation in CHIPS
 
Intervention
Eligible women will be randomised centrally to either ‘less tight’ control (aiming for dBP of 100mmHg) or ‘tight’ control (aiming for dBP of 85mmHg) of their hypertension.

Randomisation will be stratified by centre and type of hypertension (pre-existing or gestational). In the ‘less tight’ control group, if dBP is = 105mmHg, then antihypertensive medication must be started or increased in dose. In the ‘tight’ control group, if dBP is = 80mmHg, then antihypertensive medication must be decreased in dose or discontinued.

Both groups: Centres will provide their usual care. Data will be collected on potential co-interventions (e.g., hospitalisation, bed-rest).
 
Outcome measures
Primary

Pregnancy loss (miscarriage, pregnancy termination, stillbirth, or neonatal death) or NICU admission for >48hr in the first 28 days of life or prior to primary hospital discharge, whichever is later.

Secondary

One/more serious maternal complication(s) until six weeks postpartum

Power/data analysis
Reduction in pregnancy loss or ‘high level’ neonatal care for > 48hr from 33% to 25%: the final sample size of 514/group was based on a two-tailed alpha of 0.05, power of 80%, rates of the primary outcome of 33% in the ‘tight’ control group and 25% in the ‘less tight’ control group (after a crossover of 10% of patients to the alternate treatment), and two interim analyses (after 1/3 and 2/3 of patients have been evaluated for the primary outcome). The sample size was inflated by 1% to account for loss to follow-up. The sample size was calculated by chi-square using the EAST software and the Lan DeMets spending function with O'Brien-Fleming type boundaries. Note that the use of logistic regression for the primary outcome (Section 2.16) increases the statistical power of the analysis

(J Clin Epidemiol 2004;57(5):454-60’214).
This sample size will give us 78% power (alpha of 0.05, two-sided) to find an increase of 5% in adverse maternal outcome in the ‘less tight’ control group. This is based on a risk of serious maternal complications of 7% in the ‘tight’ control group, based on inclusion of additional maternal outcomes from the PIERS (Pre-eclampsia Integrated Estimate of Risk Study) project.
 

Economic evaluation

Will be performed by Canadian CHIPS study group.

Time schedule
Recruitment during a 4 year period from April 2009.

Project leaders
Dr Wessel Ganzevoort, Academic Medical Center
Prof Dr Joris van der Post, Academic Medical Center
Prof Dr Ben Willem Mol, Academic Medical Center
 

Health Technology Assessment

Not applicable

Methodology

Not applicable

Subsidy
Canadian Institute of Health Research
 
Contact
Dr Wessel Ganzevoort, Room H4-205, POBox 22660 1100 DD Amsterdam
06-24823452
chips@studies-obsgyn.nl