The ACHIEVE Trial: Achieving Longer Gestation in Preeclampsia Via Antihypertensive Therapy.

Study Overview
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Brief Summary
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The Achieve Trial is a randomized clinical trial to test whether lowering blood pressure to less than 140/90 mmHg in women with hypertensive disorders of pregnancy will prolong pregnancy.

Detailed Description
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Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are characterized by new onset high blood pressure in pregnancy and constitute a major cause of maternal and perinatal morbidity and mortality; severe hypertension (blood pressure ≥160/110 mmHg) is a common trigger for antihypertensive treatment and preterm delivery. We propose a clinical trial that will test whether lowering the blood pressure in women with hypertensive disorders of pregnancy at <36 weeks' gestation to <140/90 mmHg will prolong pregnancy and, therefore, improve maternal and fetal/neonatal outcomes. Data generated in this study, along with knowledge and skills acquired by the candidate in the complementary career development plan, will facilitate an independent research career focused on hypertension and cardiovascular disease in pregnancy.

Official Title
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The ACHIEVE Trial: Achieving Longer Gestation in Preeclampsia Via Antihypertensive Therapy.

Conditions
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Preeclampsia, Gestational Hypertension, Hypertensive Disorder of Pregnancy

Intervention / Treatment
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* Drug: Antihypertensive treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women Gestational age: 23 weeks, 0 days to 35 weeks, 6 days Hypertensive disorder of pregnancy including gestational hypertension or preeclampsia, the non-severe form at enrollment, which is called without severe features by the American College of Obstetricians and Gynecologists. No evidence of the severe form of preeclampsia, termed severe features, as outlined in maternal exclusions No indication for delivery at the time of enrollment. Planned expectant management at time of enrollment Singleton or dichorionic twin gestation, defined at and beyond 14 weeks gestation. (A pregnancy complicated by a vanishing twin in the first trimester defined as less than 14 weeks gestation will be eligible.) Dating sonogram at less than 21 weeks of gestation Prenatal care, or another healthcare visit with a documented blood pressure, at less than 21 weeks gestation Intact membranes Exclusion Criteria: Preeclampsia with severe features, defined per ACOG as: Systolic blood pressure of 160 mm Hg or more, or diastolic blood pressure of 110 mm Hg or more on two occasions at least 4 hours apart (unless antihypertensive therapy is initiated before this time) Thrombocytopenia defined as: lower than 100 x 10e9 platelets/L Impaired liver function that is not accounted for by alternative diagnoses and as indicated by abnormally elevated blood concentrations of liver enzymes (to more than twice the upper limit normal concentrations), or by severe persistent right upper quadrant or epigastric pain unresponsive to medications Renal insufficiency (serum creatinine concentration more than 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease) Pulmonary edema New-onset headache unresponsive to medication and not accounted for by alternative diagnoses Visual disturbances Underlying renal dysfunction defined as, presenting the following parameters prior to 20 weeks gestation: baseline creatinine, equal to or higher than, 1.2 mg/dL Or proteinuria: defined as presenting protein in urine, equal to or higher than, 300 mg/24 hours or protein/creatinine ratio, equal to or higher than, 0.3 or Urine dipstick reading of greater than or equal to 2 at baseline and in the absence of a urinary tract infection Stage 2 chronic hypertension Contraindications to labetalol and nifedipine XL according to the FDA package insert Patient unable to or unwilling to adhere to management recommendations Fetal Reasons for Study Ineligibility: Fetal growth restriction (lower than 10th percentile) at enrollment, based on an ultrasound within 3 weeks prior to enrollment Oligohydramnios defined by amniotic fluid deepest vertical pocket <2 cm based on an ultrasound within the 48 hours prior to enrollment Known major structural or chromosomal abnormality

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Antihypertensive treatment for a BP goal of less than 140/90 mmHg | Drug: Antihypertensive treatment<br>* Antihypertensive treatment to goal of less than 140/90 mmHg<br>|
| No Intervention: Usual Care<br>Antihypertensive treatment only if BP ≥ 160/110 mmHg | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of days from randomization to delivery | Duration of prolongation of pregnancy | From randomization to delivery, up to 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perinatal morbidity | Composite of NICU admission ≥2 days, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, or fetal or newborn death within 6 weeks after birth; individual elements of the composite, the frequency of small for gestational age neonates, birthweight. | 6 weeks | 
| Neonatal healthcare utilization | NICU and hospital length of stay | 6 weeks | 
| Maternal morbidity | Composite of severe hypertension, pulmonary edema, heart failure, eclampsia, stroke, liver dysfunction, acute renal failure, thrombocytopenia, abruption, ICU admission, postpartum hospital readmission for hypertension management, or death within 6 weeks of delivery; individual elements of the composite. | From randomization to 6 weeks after delivery, up to 20 weeks | 
| Maternal healthcare utilization | Antepartum and postpartum hospital length of stay, ICU admission, postpartum readmission. | From randomization to 6 weeks after delivery, up to 20 weeks |