Clinical trial NCT04402385: Aspirin to Prevent Preeclampsia in Women With Elevated Blood Pressure and Stage 1 Hypertension (ASPPIRE)
Official title: Aspirin to Prevent Preeclampsia in Women With Elevated Blood Pressure and Stage 1 Hypertension (ASPPIRE)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pre-Eclampsia
Stage 1 Hypertension
Elevated Blood Pressure
Keywords: Aspirin
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2020-05-26
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To determine if low dose aspirin reduces the incidence of hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome) in pregnant women with stage 1 hypertension and elevated blood pressure.

Detailed description: At the baseline visit, women will go through informed consent and review of study eligibility. Objectives of the study, participation requirements, eligibility inclusion and exclusion will be reviewed in detail. If these are not met, the woman is excluded from the study. If she meets inclusion criteria, a checklist of exclusion criteria will be reviewed. If any exclusions are met, the woman is excluded from the study. The consent form will be reviewed in detail. If the woman consents and signs all pages of the form, randomization follows.

Randomization will be done in a 1:1 allocation ratio between the treatment and placebo arms, stratified by blood pressure group (elevated blood pressure and stage 1 hypertension). A computer algorithm will assign participant based on random permuted blocks design with block size between 2-4 within each strata. Each participant will have an assigned Study ID number that is linked to their random assignment.

Participants will be contacted by telephone 1 week after randomization. The purpose of this visit is to ensure the participant has received study medication and initiated the regimen.

The third encounter will be 6 weeks (+/- 1week) after randomization in person to coincide with routine prenatal visit or via telephone. The purpose of this study visit is to review their pregnancy course, use of study medications, any side effects, difficulties with the study, and have opportunities to make comments and/or ask questions. The participants will be asked to bring their study medication for pill count at the time of this encounter, if the study visit is able to be performed in person. Study participants will continue their routine prenatal care with pregnancy management performed routinely per their provider.

The fourth encounter will be 16 weeks (+/- 1week) after randomization in person to coincide with routine prenatal visit or via telephone. If the participant is already delivered by this time, the visit will be performed via telephone postpartum. The purpose of this study visit is to review their pregnancy course, use of study medications, any side effects, difficulties with the study, and have opportunities to make comments and/or ask questions. The participants will be asked to bring their study medication for pill count at the time of this encounter, if the study visit is able to be performed in person.

The rest of the study will be conducted via chart review. Each prenatal visit will be reviewed for blood pressure, evaluation of symptoms, review of any laboratory and/or imaging results. New diagnoses, medications, and hospital admissions will be documented.

Delivery records will be abstracted for outcomes listed below. Neonatal records will be reviewed from birth until 1 year of age. Neonatal and infant chart abstraction will include birthweight, Apgar scores, hospital course, problem visit, diagnoses, medications, emergency department visits, and hospitalizations. Participant's postpartum course will be reviewed for 1 year postpartum, including outpatient visits, emergency department visits, and any hospitalizations.

The study will be performed by an intent-to-treat analysis. Thus, even women who discontinue study medication will be included in final analyses.

Eligibility criteria: Inclusion Criteria:

* Singleton pregnancy
* Elevated blood pressure (At least 2 systolic BP 120-129 mm Hg within 1 year pre-pregnancy until 20 weeks gestational age on at least 2 separate healthcare encounters) or Stage 1 hypertension (At least 2 systolic BP 130-139 and/or diastolic BP 80-89 within 1 year pre-pregnancy until 20 weeks gestational age on at least 2 separate healthcare encounters)
* Speaks English or Spanish
* Informed and written consent
* Confirmed single live intrauterine pregnancy (confirmed by positive cardiac motion by transvaginal or transabdominal ultrasound)

Exclusion Criteria:

* Chronic hypertension
* Pre-gestational diabetes
* Chronic renal disease

  - diagnosis of stage 1 chronic kidney disease or higher and/or GFR \<60 mL/min with duration at least 3 months and/or history of kidney transplantation and/or undergoing peritoneal or hemodialysis
* Systemic lupus erythematous
* Antiphospholipid antibody syndrome (diagnosis made by having 1 or more clinical criteria and 1 or more laboratory criteria)

  * Clinical criteria: venous thrombosis, arterial thrombosis, obstetric complications (3 or more unexplained consecutive spontaneous abortions \<10 weeks gestation, 1 or more unexplained deaths of a morphologically normal fetus after 10 weeks gestation, 1 or more premature births before 34 weeks gestation attributable to placental insufficiency, including severe preeclampsia or fetal growth restriction)
  * Laboratory criteria: lupus anticoagulant, anti-cardiolipin IgG or IgM with titer \>99th percentile, anti-beta 2 glycoprotein IgG or IgM with titer \>99th percentile. Laboratory result must be positive twice at least 12 weeks apart
* Multifetal gestation
* 20 weeks gestation at time of randomization based on American College of Obstetricians and Gynecologists dating criteria. Dating will be based on last menstrual period (LMP) if regular, sure LMP is available that agrees with ultrasound dating. Otherwise, earliest ultrasound will be used for dating purposes.
* Prior history of hypertensive disorder of pregnancy
* Current pregnancy with known chromosomal, genetic, major malformations or fetal demise, or planned termination of pregnancy
* Women with contraindications to taking aspirin (bleeding diathesis such as Von Willebrand's disease, peptic ulcer disease, aspirin hypersensitivity, nasal polyps, asthma with aspirin-induced bronchospasm, severe liver disease).
* Concurrent participation in another study that influences risk of preeclampsia
* Women who do not plan to deliver within the YNHH system

Primary outcomes:
measure: Development of Hypertensive Disorder
timeFrame: after 20 weeks gestation until 6 weeks postpartum
Secondary outcomes:
measure: Development of Gestational Hypertension
timeFrame: after 20 weeks gestation until 6 weeks postpartum
measure: Development of Preeclampsia
timeFrame: after 20 weeks gestation until 6 weeks postpartum
measure: Development of Preeclampsia- 37 Weeks
timeFrame: up to 37 weeks gestation
measure: Development of Preeclampsia- 34 Weeks
timeFrame: up to 34 weeks gestation
measure: Development of Eclampsia
timeFrame: after 20 weeks gestation until 6 weeks postpartum
measure: Development of HELLP Syndrome
timeFrame: after 20 weeks gestation until 6 weeks postpartum
measure: Spontaneous Preterm Delivery
timeFrame: Up to 37 weeks
measure: Spontaneous Preterm Delivery
timeFrame: Up to 34 weeks
measure: Fetal Growth Restriction
timeFrame: after 20 weeks gestation until delivery
measure: Birthweight
timeFrame: day of life 0
measure: Neonatal ICU Admission
timeFrame: Birth until 1 year of age
measure: Stillbirth
timeFrame: after 20 weeks gestation until delivery
measure: Neonatal Adverse Events
timeFrame: Birth until 1 year of age
measure: Placental Abruption
timeFrame: after 20 weeks gestation until delivery
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Olga Grechukhina, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Hillart Hosier, MD
role: PRINCIPAL_INVESTIGATOR
References: