The Chronic hypertension and Pregnancy (CHAP) project is a large pragmatic multi-center randomized clinical trial designed to evaluate the comparative effectiveness and safety of pharmacologic treatment of mild chronic hypertension (CHTN) in pregnancy. During pregnancy, CHTN is the most common major medical disorder, most often mild (BP <160/110 mmHg), and associated with a 3-5 fold increase in adverse outcomes including preeclampsia, perinatal death, preterm birth (PTB) and small for gestational age (SGA) infants (birth weight <10th percentile). Whereas antihypertensive therapy is a public health priority for the general population, authorities, including the American College of Obstetricians and Gynecologists (ACOG), recommend against BP lowering therapy during pregnancy unless hypertension is severe, i.e., e160/110 mm Hg, because of uncertain benefits and the concern that therapy may actually increase the risk of SGA. Based on supportive preliminary data presented herein, we hypothesize that antihypertensive therapy for CHTN during pregnancy to the goal <140/90 mmHg as currently recommended for the non-pregnant hypertensive population, will reduce the risk of several adverse pregnancy outcomes including SGA. During a 6-year project period, our consortium of 12 academic perinatal centers (25 sites), will identify 4700 women with mild CHTN and BP<155/100 mmHg (which providers are more comfortable not treating) in early pregnancy and randomize them to either antihypertensive therapy (using labetalol) or to management according to ACOG recommendations (antihypertensive therapy for more severe CHTN). The women will be followed-up until discharge from the {hospital after delivery and up to 3 months postpartum (longer follow-up is anticipated separately; contingency funds will be considered for interim 6-month phone call). The following Specific Aims will be addressed: } {1.1 Primary Aim: To determine if pharmacologic treatment of mild CHTN in pregnancy to a standardized BP} goal<140/90 mmHg, compared with standard management (per ACOG: no treatment unless hypertension is severe), reduces the risk of adverse pregnancy outcomes including: 1) a severe perinatal composite outcome (perinatal death, severe preeclampsia, placental abruption or indicated PTB <35 weeks) and 2) SGA. 1.2 Secondary Aims: i. To better quantify the risks of severe maternal cardiovascular outcomes associated with mild CHTN during pregnancy and determine the impact of treatment. ii. To investigate the optimal gestational age to deliver women with CHTN in order to minimize maternal and perinatal complications. We will apply survival analysis methods to the trial population. iii. To collect and store biospecimens including maternal blood, cord blood and placentas for future biological and biophysical studies to understand the effects of antihypertensive therapy in pregnant women with mild CHTN. iv. To assess whether antihypertensive treatment of mild CHTN during pregnancy increases post-pregnancy adherence to recommended therapy.
The Chronic Hypertension and Pregnancy (CHAP) Project is a large pragmatic multi-center randomized trial designed primarily to evaluate the benefits and harms of antihypertensive therapy for mild chronic hypertension in pregnancy to a goal <140/90 mmHg (as recommended for the general population in the US) compared with ACOG's current policy to withhold treatment unless hypertension is severe. The trial will be conducted in 12 experienced research-oriented Ob/Gyn departments (including 25 clinical sites) in the United States. The monitoring plan includes a pre-specified option to increase the planned sample size of 4700 if necessary after interim evaluation by an independent Data Safety and Monitoring Board.
