Aspirin for Miscarriage and Preeclampsia
(APPLE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: University of Pennsylvania
Must be taking: Aspirin
Must not be taking: Anticoagulants, NSAIDs
Disqualifiers: Aspirin allergy, Anticoagulant need, others
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?The goal of this clinical trial is to investigate the effects of early initiation of double low-dose aspirin in pregnant women. The main questions it aims to answer are:
Does this dose and timing of aspirin reduce the risk of pre-eclampsia compared to standard recommendations? Does this dose and timing of aspirin reduce the risk of pregnancy loss compared to standard recommendations? Participants will begin taking at no later than 6 weeks 6 days gestational age, either 162mg of aspirin through delivery or placebo until 12 weeks and then 81mg of aspirin through delivery.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, if you are on anticoagulant therapy or need to use NSAIDs regularly during pregnancy, you may not be eligible to participate.
What data supports the effectiveness of the drug aspirin for preventing miscarriage and preeclampsia?
Research shows that aspirin can help prevent preeclampsia (a pregnancy complication characterized by high blood pressure) in high-risk patients, and it has been used safely during pregnancy in low doses. However, its benefits for preventing unexplained recurrent miscarriages have not been clearly demonstrated.
12345Is low-dose aspirin safe for pregnant women?
Low-dose aspirin is generally considered safe for pregnant women, especially when used to prevent preeclampsia in those at high risk, as long as the daily dose does not exceed 100mg.
12367How does aspirin differ from other drugs for miscarriage and preeclampsia?
Aspirin is unique because it is used in low doses to prevent preeclampsia and miscarriage by reducing platelet activity and improving blood flow to the placenta. Unlike other treatments, aspirin is recommended for women at high risk of preeclampsia, with specific guidelines on dosage and timing to maximize its effectiveness.
12389Eligibility Criteria
The APPLE trial is for pregnant women who can start treatment no later than 6 weeks and 6 days into their pregnancy. It's designed to see if early aspirin use can prevent complications like pre-eclampsia or pregnancy loss. Women with certain health conditions or on conflicting medications may not be eligible.Inclusion Criteria
I can take pills and will follow the aspirin plan.
Provision of signed and dated informed consent form
Patients with a gestation less than or equal to 6 weeks, 6 days (as determined by patient record of LMP or ART date)
+2 more
Exclusion Criteria
I cannot take aspirin due to asthma, nasal polyps, bleeding disorders, or past stomach ulcers.
I have severe pelvic pain or heavy bleeding needing urgent care.
Known allergies to aspirin or non-steroidal anti-inflammatory agents (NSAID)
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants begin taking either 162mg of aspirin or placebo until 12 weeks, then 81mg of aspirin through delivery
From enrollment to delivery, approximately 38 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
This study tests whether taking a double low-dose of aspirin (162mg) daily from very early in pregnancy, compared to a standard dose (81mg after the first trimester), reduces the risk of developing pre-eclampsia or experiencing pregnancy loss.
2Treatment groups
Active Control
Placebo Group
Group I: Double low-dose aspirinActive Control1 Intervention
Participants will take 2 81mg aspirin tablets daily from entrance into the trial until delivery.
Group II: Standard of CarePlacebo Group1 Intervention
Participants will take 2 placebo pills from entrance into the study until 12 weeks gestational age, they will then take 1 placebo pill and 1 81mg aspirin until delivery.
Aspirin is already approved in European Union, United States, Canada, China for the following indications:
🇪🇺 Approved in European Union as Aspirin for:
- Pain relief
- Fever reduction
- Inflammation
- Cardiovascular disease prevention
- Preeclampsia prevention
🇺🇸 Approved in United States as Aspirin for:
- Pain relief
- Fever reduction
- Inflammation
- Cardiovascular disease prevention
- Preeclampsia prevention
🇨🇦 Approved in Canada as Aspirin for:
- Pain relief
- Fever reduction
- Inflammation
- Cardiovascular disease prevention
- Preeclampsia prevention
🇨🇳 Approved in China as Aspirin for:
- Pain relief
- Fever reduction
- Inflammation
- Cardiovascular disease prevention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PennsylvaniaPhiladelphia, PA
Loading ...
Who Is Running the Clinical Trial?
University of PennsylvaniaLead Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Collaborator
References
[The Role of Aspirin in Preeclampsia Prevention: State of the Art]. [2018]The role of acetyl salicylic acid (ASA or aspirin) in preeclampsia prevention and in other complications has been subject to studies and controversies for the last 30 years. The first research results concerning the role of placenta in preeclampsia have been published by the end of seventies and they showed an increase in the platelet activity and a prostaglandin synthesis disturbance, as a consequence of a deficient placentation. In the last twenty years of the XX century important studies were published on the aspirinprophylactic role in preeclampsia risk reduction.
Leveraging quality improvement to promote health equity: standardization of prenatal aspirin recommendations. [2023]Aspirin (ASA) is recommended for patients at elevated risk of preeclampsia. Limited data exists on adherence to guidelines for ASA prescription. This project evaluates the implementation of a standardized approach to ASA prescription in an academic OB/Gyn practice.
[Aspirin: Indications and use during pregnancy]. [2018]Aspirin (acetylsalicylic acid) has been used ever since the Antiquity for its painkilling and anti-inflammatory effects. Its antiplatelet properties have then extended its indications to the field of coronaropathy and vascular cerebral disease, and finally to vascular placental disease. Aspirin has been widely prescribed since the 1980's to prevent pre-eclampsia, intra-uterine growth retardation and fetal death of vascular origin. It has also been proposed to prevent unexplained recurrent miscarriages. Its use during pregnancy is considered as safe, provided the daily doses do not exceed 100mg. Aspirin has been proven efficient to prevent pre-eclampsia and fetal growth restriction in high-risk patients. The benefits of prescribing aspirin have been demonstrated neither for vascular placental disease prevention in low risk patients, nor in cases of unexplained recurrent miscarriages.
First trimester screening for preeclampsia. [2016]Aspirin therapy from the first trimester of pregnancy may benefit women at high risk for preeclampsia. We review publications from the past year that examine first-trimester screening studies for preeclampsia.
Low-dose aspirin in primigravidae with positive roll-over test. [2018]In a prospective, randomized, double-blind study for the prevention of pregnancy-induced hypertension and preeclampsia, 41 primigravidae with positive roll-over test (28th-32nd week of pregnancy) received 80 mg aspirin/day or placebo until the end of the 37th week. In the patients treated with acetylsalicylic acid (n = 22), 3 cases of proteinuria occurred, but no hypertensive pregnancy complication. In the placebo group (n = 19), 10 patients developed pregnancy-induced hypertension (6 of them preeclampsia). Group-specific differences concerning the occurrence of hypertension were statistically highly significant (p = 0.0004). No relevant differences were observed with regard to pregnancy duration, birth weight and umbilical artery pH value. The placebo group included 1 intrauterine death. No increased tendency to maternal or fetal bleeding was noticed.
Low-dose aspirin therapy in obstetrics. [2019]The results of four large controlled clinical trials, encompassing over 13,000 pregnant women, indicate that low-dose aspirin is of benefit in the prevention of pre-eclampsia in women at high risk. The preventive effect on fetal growth retardation seems to be small, and no therapeutic benefits could be established. Low-dose aspirin appears to be safe for mother, fetus, and neonate.
Should we recommend universal aspirin for all pregnant women? [2022]Low-dose aspirin has been demonstrated to reduce the incidence of preeclampsia and fetal growth restriction in at-risk populations. Its role in low-risk populations is as yet unknown. Novel preeclampsia screening tests are emerging that can predict the risk of the development of preeclampsia from as early as 11 weeks of gestation. It may be more efficacious, acceptable, and cost-effective to prescribe low-dose aspirin to all pregnant women from the first trimester as opposed to performing a screening test in the first instance. There is variation in opinion: the American College of Obstetricians and Gynecologists suggests the use of aspirin only in women who are at risk of preeclampsia, based on patient history; the National Institute for Health and Clinical Excellence, UK, and the US Preventative Services Task Force recommend the use of low-dose aspirin if there is 1 major or 2 moderate risk factors. This point-counterpoint discussion shall address (1) controversies regarding the real impact of low-dose aspirin; (2) controversies in the actual guidelines among the different national societies; (3) controversies regarding emerging preeclampsia screening tests in terms of cost-effectiveness and efficacy, and (4) points in favor of the provision of universal vs screened-positive women.
Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review. [2019]To examine the effectiveness of aspirin in preventing perinatal death and preeclampsia in women with predisposing historical risk factors, such as previous history of preeclampsia, chronic hypertension, diabetes, and renal disease.
Low-dose aspirin therapy for the prevention of preeclampsia: time to reconsider our recommendations? [2023]The American College of Obstetricians and Gynecologists recommends initiation of 81 mg of aspirin daily for women at risk of preeclampsia between 12 and 28 weeks' gestation, optimally before 16 weeks, with continuation until delivery. The World Health Organization recommends that 75 mg of aspirin should be initiated before 20 weeks of gestation for women at high risk of preeclampsia. Both the Royal College of Obstetricians and Gynaecologists and the National Institute of Health and Care Excellence quality statement on "Antenatal Assessment of Pre-eclampsia Risk" request that healthcare providers prescribe low-dose aspirin to pregnant women at increased risk of preeclampsia daily from 12 weeks of gestation. The Royal College of Obstetricians and Gynaecologists recommends 150 mg of aspirin daily, and the National Institute of Health and Care Excellence guidelines suggest risk stratification with a dosage of 75 mg for those at moderate risk of preeclampsia and 150 mg for those at high risk of preeclampsia. The International Federation of Gynecology and Obstetrics initiative on preeclampsia recommends 150 mg of aspirin to be initiated at 11 to 14+6 week's gestation and also proposes that 2 tablets of 81 mg is an acceptable alternative. Review of the available evidence suggests that both the dosage and timing of aspirin initiation is key to its effectiveness at reducing the risk of preeclampsia. Doses of >100 mg of aspirin daily initiated before 16 weeks' gestation seem to be most effective at reducing the risk of preeclampsia and thus dosages recommended by most major societies and organizations may not be effective. Randomized control trials examining 81 mg vs 162 mg of aspirin daily for the prevention of preeclampsia are required to assess the safety and efficacy of aspirin dosages available in the United States.