Chronic Hypertension and Pregnancy (CHAP) Project

Purpose

The purpose of this study is to evaluate whether a blood pressure treatment strategy during pregnancy to achieve targets that are recommended for non-pregnant reproductive-age adults (<140/90 mmHg) compared ACOG- recommended standard during pregnancy (no treatment unless BP is severe) is effective and safe.

Condition

  • Hypertension

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

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:
  6. Class C or higher diabetes mellitus
  7. 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

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Anti-hypertensive therapy to goal <140/90 mmHg
Labetalol or Nifedipine ER will be used as first-line to achieve goal; if necessary Nifedipine ER or Labetalol will be second-line antihypertensive. Rarely, other antihypertensive medications may also be used
  • Drug: Anti-hypertensive therapy
    1st line anti-hypertensive (Labetalol or Nifedipine ER) started; escalate to maximum dose and a preferred 2nd line medication if needed (nifedipine ER or Labetalol)
    Other names:
    • Normodyne
    • Trandate
    • Procardia XL
    • Adalat
Active Comparator
No anti-hypertensive unless BP is severe (≥160/105 mmHg
Antihypertensive therapy given only if BP becomes severe (defined as BP ≥160/105). The lowest dose of anti-hypertensive needed to keep blood pressure below this threshold will be given (1st-line - Labetalol or Nifedipine ER and 2nd-line - Labetalol or Nifedipine ER). Rarely other medications may be used
  • Other: No anti-hypertensive therapy (unless BP is severe)
    Treatment will not be started if blood pressure remains <160/105; for blood pressure ≥160/105, treatment with labetalol or Nifedipine ER will be initiated and maintained at lowest dose needed to keep blood pressure under 160/105.

Recruiting Locations

UT Medical Branch
Galveston, Texas 77555
Contact:
George R Saade, MD
409-747-0482
gsaade@utmb.edu

More Details

NCT ID
NCT02299414
Status
Recruiting
Sponsor
University of Alabama at Birmingham

Study Contact

Alan Tita, MD, PhD
205-934-5612
atita@uabmc.edu

Detailed Description

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.