The CHIPS Trial (Control of Hypertension In Pregnancy Study)

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 to inform clinical
decision-making. Therefore, we propose the CHIPS Trial.

For pregnant women with non-severe non-proteinuric maternal hypertension at
14-33 weeks, will *less tight* control (target dBP of 100mmHg) vs. *tight*
control (target dBP of 85mmHg) increase or decrease the likelihood of pregnancy
loss or neonatal intensive care unit (NICU) admission for more than 48hr?

The CHIPS Trial is an international multicentre RCT that will recruit 1,028
women (514/group) from 50 tertiary and community centres over 4 years. 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).
The primary outcome will be compared between groups using adjusted logistic
regression (alpha of 0.046, two-sided). Two interim analyses are planned after
primary outcome data are available for 1/3 and 2/3 of enrolled women; our
independent Data Safety Monitoring Board will use p<0.0002 and p<0.012,
two-tailed, as guidelines for considering early termination of the trial at the
first and second interim analyses, respectively.
Follow-up: Outcome data will be collected during the woman*s (and baby*s)
hospital stay for birth (or loss). Women will be contacted at approximately six
weeks after delivery (or loss) to enquire about satisfaction with care,
disruption of home or family life, any major maternal/neonatal morbidity
following hospital discharge, and views about BP management.

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).
Compliance (dBP and antihypertensive dose) will be assessed at two weeks (± 7
days) after randomisation.

Patients are subjected to either treatment stategy, both of which are standard
practice in the Netherlands. In that sense there is no additional burden.
however, blood pressure will be measured according to guidelines. This will
take a few minutes more time, but will actually result in improvement of care,
because standard practice is suboptimal measurement of blood pressure.
Additional burden is in the diary that is kept by the patient to record all
visitis to professionals involved in the prenatal care; also patients will be
called several times to keep track of the events in pregnancy.