Chronic Hypertension and Pregnancy (CHAP) Project

During pregnancy, chronic hypertension (CHTN) is the most common major medical disorder
encountered, occurring in 2-6%. The substantial negative effect of CHTN on pregnancy includes
a consistent 3- to 5-fold increase in superimposed preeclampsia and adverse perinatal
outcomes (fetal or neonatal death, preterm birth -PTB, poor fetal growth and placental
abruption) and possibly a 5- to10-fold increase in maternal cardiovascular and other
complications (death, cerebrovascular accident, pulmonary edema and acute renal failure).
Mild CHTN (BP <160/110) contributes to a large proportion of these adverse outcomes. While
antihypertensive treatment of CHTN is standard for the general population, it is uncertain
whether treatment during pregnancy reduces maternal or fetal complications, and there are
concerns that decreased arterial pressure may reduce fetal blood flow and cause poor fetal
growth or small-for-gestational-age (SGA) infants. Some authorities, including the American
College of Obstetricians and Gynecologists (ACOG) and American Society of Hypertension (ASH)
recommend withholding antihypertensive therapy for mild CHTN, particularly if BP is
<160/105-110 mmHg. The recommendation to withhold antihypertensive treatment in pregnancy
conflicts with the broader public health goal to reduce BP in those with CHTN and there is no
evidence that discontinuing therapy during the brief period of pregnancy affects maternal
outcomes (other than reducing the severe hypertension). For over a decade, authorities have
consistently called for well-designed and powered trials to delineate the benefits and risks
of pharmacologic therapy for CHTN during pregnancy.

Therefore, our multicenter consortium proposes the Chronic Hypertension and Pregnancy (CHAP)
Project, a large pragmatic randomized trial with a primary aim to evaluate the benefits and
harms of pharmacologic treatment of mild CHTN in pregnancy.

Inclusion Criteria:

1. Women with chronic hypertension in pregnancy with new or untreated chronic
hypertension, blood pressure 140-159 systolic or 90-104 diastolic OR known chronic
hypertension on monotherapy and taking any antihypertensive and blood pressure
≤159/104 (including those with blood pressure <140/90);

2. Singleton; and

3. viable pregnancy <23 weeks of gestation.

Exclusion Criteria:

1. Blood pressures prior to randomization ≥160 systolic or ≥105 diastolic (with or
without treatment);

2. Patients currently treated with >1 antihypertensive medication (more likely to have
severe chronic hypertension);

3. Multi-fetal pregnancy;

4. Known secondary cause of chronic hypertension;

5. High-risk co-morbidities for which treatment may be indicated:

- Class C or higher diabetes mellitus

- Chronic kidney disease - including baseline proteinuria (>300mg/24-hr, p/c ratio
>0.3, or persistent 1+ proteinuria*) or creatinine >1.2.

*If a dipstick value at screening is more than trace, a clean catch or catheter
urine should be obtained and re-tested by dipstick. If this shows trace or
absence of protein, the patient is included. If it again shows 1+ protein, the
patient is excluded until a 24-hr urine <300mg/24hr or p/c ratio is <0.3.

- Cardiac disorders: cardiomyopathy, angina, CAD

- Prior stroke

- Retinopathy

- Sickle cell disease;

6. Known major fetal anomaly;

7. Known fetal demise;

8. Suspected IUGR;

9. Membrane rupture or planned termination prior to randomization;

10. Plan to deliver outside the consortium centers (unless approved by the Clinical
Coordinating Center) or unlikely to follow-up in the opinion of study staff or
previous participation in this trial;

11. Contraindication to labetalol or nifedipine (e.g. know hypersensitivity); and (12)
Current substance abuse or addiction (cocaine, methamphetamine) *The minimum age
varies by center