Low Doses of Aspirin in the Prevention of Preeclampsia (ASAPP)
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| ClinicalTrials.gov Identifier: NCT04070573 |
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Recruitment Status :
Enrolling by invitation
First Posted : August 28, 2019
Last Update Posted : December 15, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Preeclampsia | Drug: acetylsalicylic acid | Phase 3 |
Preeclampsia (PE) is a serious and potentially fatal complication of pregnancy. It is a placental disease characterized by an elevated blood pressure in the 3rd trimester with multisystem involvement (proteinuria, elevated liver enzymes, low platelet count and/or neurologic symptoms). PE can cause pulmonary edema, seizures, or stroke and is a leading cause of maternal mortality. The pregnancy outcomes are further worsened if PE develops before term. Women who have a history of PE in a prior pregnancy, diabetes, preexisting hypertension, kidney disease, multifetal gestation or autoimmune diseases are at an increased risk to develop PE in a subsequent pregnancy.
Clinical trials evaluating the benefits of low-dose aspirin (ASA) have used a wide range of doses from 60mg to 150mg orally daily with low-dose being defined as less than 325mg per day. Taking ASA (as opposed to placebo) is thought to reduce the risk of preeclampsia by 17%, without increasing the risk of major obstetric bleeding. The number needed to treat is only 19 women. ASA is currently the only prophylactic therapy for PE in high-risk women to be recognized by the US Preventive Task Force and should be initiated early in the second trimester of pregnancy, before 16 weeks of gestation.
There has also been more awareness that the efficacy of ASA in preventing preeclampsia is limited by the poor adherence of patients to this therapy. Indeed, a cross-sectional study has estimated that up to 46% of women (n=42) on ASA therapy may not be compliant to it, as determined by a validated Simplified Medication Adherence Questionnaire (SMAQ). Adherence is essential to the efficacy of ASA in preventing preterm preeclampsia. It would therefore be of interest to obtain more information about adherence to ASA in women who need this therapy.
Assessing molecular pathways in the development of PE may allow opportunity for earlier diagnosis, specific triaging of patients to closer monitoring and further development of preventative or curative treatment strategies. Samples will be biobanked for biomarker discovery in the future.
The current literature is lacking in evidence to recommend a specific daily dose of ASA. Recent meta-analyses have suggested that there may be a dose response in the protective effect of ASA for PE. As compared to 60mg per day, an ASA dose of 100mg per day was associated with a lower relative risk of PE (0.44 vs 0.57, p=0.36). A large study of 1776 women has compared a slightly higher dose of ASA (150mg per day) to placebo and found a decrease in preterm delivery (before 37 weeks) due to PE (OR 0.38, p=0.004). Meta-analyses have shown that any dose of ASA above 60mg per day is protective and should be used to prevent PE in high risk pregnancies.
To date, there has not been any studies comparing lower doses of ASA (such as 81mg, the traditional "baby aspirin" dose sold in the US) to higher "low-dose" ASA regimens (such as 162mg) in their ability to prevent preterm or severe PE in women who are at a high risk for this devastating disease.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 400 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Arm 1: 81mg oral ASA daily. Arm 2: 162mg oral ASA daily. Patients will obtain their prescriptions from their respective pharmacies. Women in Arm 1, will be instructed to take one table of 81mg aspirin per day; those in Arm 2, will be asked to take two tablets simultaneously orally once per day. Therapy will be initiated at the baseline visit and continued until 1 week before planned delivery or upon admission for unplanned/imminent delivery as per clinical routine. |
| Masking: | None (Open Label) |
| Masking Description: | This is an open label randomized controlled trial. |
| Primary Purpose: | Prevention |
| Official Title: | A Randomized Controlled Trial Comparing Low Doses Of Aspirin In The Prevention Of Preeclampsia (ASAPP) |
| Actual Study Start Date : | October 21, 2019 |
| Estimated Primary Completion Date : | August 2024 |
| Estimated Study Completion Date : | August 2024 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 81mg ASA
Patients in Arm 1, will be instructed to take one tablet of 81mg aspirin per day.
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Drug: acetylsalicylic acid
High risk pregnant women will be treated with daily aspirin during pregnancy.
Other Names:
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Active Comparator: 162mg ASA
Patients in Arm 2, will be instructed to take two tablets simultaneously orally once per day.
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Drug: acetylsalicylic acid
High risk pregnant women will be treated with daily aspirin during pregnancy.
Other Names:
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- Incidence of preterm (<37 weeks) preeclampsia [ Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum) ]The incidence of preterm (<37 weeks) preeclampsia in high risk pregnant women treated with either 81 mg or 162 mg of daily aspirin during pregnancy.
- Incidence of preeclampsia with severe features [ Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum) ]The incidence of preeclampsia with severe features (American College of Obstetricians and Gynecologists [ACOG] 2019 definition) in high risk pregnant women treated with either 81 mg or 162 mg of daily aspirin during pregnancy.
- Aspirin adherence [ Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum) ]Evaluate and compare the adherence of pregnant women to 81mg and 162mg of daily low-dose aspirin using a validated, Simplified Medication Adherence Questionnaire (SMAQ).
- Maternal and Fetal Outcomes [ Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum) ]Compare maternal and fetal outcomes in pregnant women at a high risk for preeclampsia who are treated with either 81mg or 162mg of daily aspirin during pregnancy, including preeclampsia ≥37 weeks, severe maternal hypertension, preterm delivery, fetal growth restriction, placental abruption and maternal/fetal mortality.
- Time-to-event for preeclampsia and gestational age at onset of PE [ Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum) ]Compare the time-to-event for developing preeclampsia for women treated with 81mg vs 162mg of aspirin per day. The time to event analysis will be made using the gestational age at the onset of preeclampsia as a variable
- Aspirin compliance [ Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum) ]To assess the compliance to low dose aspirin in pregnant women that are at high risk for preeclampsia and compare compliance rates for women on 81mg vs 162mg of aspirin per day using urine studies for salicylates and serum analysis.
- Impact of co-morbidities on incidence of preeclampsia [ Time Frame: 9 months for each patient (from recruitment until 6 weeks postpartum) ]Assess the impact of specific co-morbidities (diabetes, chronic hypertension, renal disease and autoimmune disease), blood pressure control, age and race on the relationship between treatment group (81mg vs 162mg aspirin per day) and preeclampsia incidence.
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| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Patients are currently only being enrolled at the New York Presbyterian Weill Cornell Medicine and at the New York Presbyterian Queens campuses.
Inclusion Criteria:
Pregnant patients, ≥18 years old, at less than 16 weeks' gestation (as documented by ultrasound) with at least one of the following risk factors for developing PE:
- PE in a prior pregnancy
- Chronic hypertension (prior to pregnancy or before 20 weeks' gestation)
- Type 1 or 2 diabetes
- Renal disease (proteinuria ≥300mg/day or estimated GFR<90mL/min/1.73 m2)
- Multifetal gestation
- Autoimmune disease (e.g. systemic lupus erythematous, antiphospholipid syndrome)
Exclusion Criteria:
- Patient with known intention to terminate pregnancy
- Major fetal malformation seen on ultrasound
- Contraindication to ASA therapy (including but not limited to allergy and high bleeding risk)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04070573
| United States, New York | |
| New York Presbyterian - Weill Cornell | |
| New York, New York, United States, 10065 | |
| New York Presbyterian Queens | |
| New York, New York, United States, 11355 | |
| Principal Investigator: | Line Malha, MD, MS | Weill Medical College of Cornell University |
| Responsible Party: | Weill Medical College of Cornell University |
| ClinicalTrials.gov Identifier: | NCT04070573 |
| Other Study ID Numbers: |
19-05020160 |
| First Posted: | August 28, 2019 Key Record Dates |
| Last Update Posted: | December 15, 2022 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Preterm preeclampsia Preeclampsia with severe features High risk pregnancy |
Low dose aspirin Cell free RNA Compliance |
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Pre-Eclampsia Hypertension, Pregnancy-Induced Pregnancy Complications Aspirin Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs |
Anti-Inflammatory Agents Antirheumatic Agents Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Platelet Aggregation Inhibitors Cyclooxygenase Inhibitors Enzyme Inhibitors Antipyretics |