Aspirin for the Prevention of Preeclampsia and Pregnancy outcomes in nulliparous women after Assisted Reproductive Technology.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

2 Aug 2023 → ongoing

Decision date (initial)

2022-10-18

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

Evaluate the effect of aspirin 150mg daily initiated between 9 and 15(+6 days) weeks of gestation versus placebo in the prevention of preterm (<37 weeks of gestation) preeclampsia in nulliparous pregnant women after assisted reproductive technology.

Secondary objectives 12

1. Compare the effect of aspirin 150mg daily initiated between 9 and 15 (+6 days) weeks of gestation versus placebo on spontaneous and total preterm birth <34 weeks of gestation.
2. Compare the effect of aspirin 150mg daily initiated between 9 and 15 (+6 days) of gestation versus placebo on spontaneous and total preterm birth <37 weeks of gestation.
3. Compare the effect of aspirin 150mg daily initiated between 9 and 15 (+6 days) weeks of gestation versus placebo on occurrence of preeclampsia <34 weeks of gestation, term preeclampsia (≥ 37 weeks of gestation).
4. Compare the effect of aspirin 150mg daily initiated between 9 and 15 (+6 days) weeks of gestation versus placebo on occurrence of cesarean delivery, postpartum hemorrhage (>500ml), placental abruption.
5. Compare the effect of aspirin 150mg daily initiated between 9 and 15 (+6 days) weeks of gestation versus placebo on occurrence of severe maternal morbidity.
6. compare the effect of aspirin 150mg daily initiated between 9 and 15 (+6 days) weeks of gestation versus placebo on occurrence of neonatal adverse outcomes: still birth, neonatal death, neonatal complications.
7. Compare the effect of aspirin 150mg daily initiated between 9 and 15 (+6 days) weeks of gestation versus placebo on birthweight.
8. Assess the overall safety of aspirin 150mg daily initiated between 9 and 15 (+6 days) weeks of gestation in nulliparous pregnant women after assisted reproductive technology.
9. Document the adherence to treatment.
10. Assess the cost of care of patients in each arm.
11. Assess the efficiency of aspirin 100mg initiated between 9 and 15 (+6 days) weeks of gestation compared with placebo using a cost-effectiveness analysis from the collective perspective
12. Assess the impact of socioeconomic characteristics on the cost of care and the efficiency.

Conditions and MedDRA coding

Preeclampsia during pregnancy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Nulliparous women aged 18 years or more
2. Pregnancy following ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), oocyte donation or intrauterine insemination with sperm donor
3. Singleton pregnancy
4. Evolutive pregnancy between 9 and 15 (+6 days) weeks of gestation
5. Women affiliated to a French Social Security Insurance or equivalent social protection
6. Written informed consent

Exclusion criteria 5

1. Major fetal abnormality
2. Regular treatment with aspirin (including antiphospholipid syndrome)
3. Aspirin contraindications (allergy, von Willebrand disease, peptic ulceration, hemophilia)
4. Women protected by law.
5. Patient included in another drug study or another interventional study which could interfere with the results of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of preterm (<37 weeks of gestation) preeclampsia (binary variable yes/no).

Secondary endpoints 16

1. Occurrence of spontaneous and total preterm birth (defined by delivery at <34 weeks of gestation)
2. Occurrence of spontaneous and total preterm birth (defined by delivery at <37weeks of gestation)
3. Occurrence of term (≥37 weeks) preeclampsia.
4. Occurrence of preeclampsia before 34 weeks of gestation.
5. Occurrence of cesarean delivery.
6. Occurrence of postpartum hemorrhage (>500ml)
7. Occurrence of placental abruption
8. Occurrence of stillbirth
9. Birthweight
10. Occurrence of severe maternal morbidity (occurrence of at least one of the following: severe postpartum hemorrhage (>1000ml), treatment of postpartum hemorrhage by embolization, vascular ligature, hysterectomy, secondary post-partum hemorrhage, pulmonary embolism, cardiovascular complications, neuropsychological complications, maternal transfer to intensive care unit, maternal death).
11. Neonatal death (before 28 days of life) or occurrence of neonatal complications including intraventricular hemorrhage grade II or above, sepsis with confirmed bacteremia in cultures, anemia requiring blood transfusion, respiratory distress syndrome treated with surfactant and ventilation, necrotizing enterocolitis requiring surgery, intensive care unit admission, ventilation with positive airway pressure or intubation.
12. Occurrence of maternal expected adverse events (any bleeding, headache, nausea, skin rash, dyspepsia, abdominal pain) recorded from randomization and until hospital discharge after delivery
13. Adherence to the treatment (by counting the pills at each visit and by using a diary or an application).
14. Number of consumed resources and unit costs of hospitalizations, consultations, medical acts, medication, medical devices and transportation.
15. Incremental cost-effectiveness from the collective perspective expressed in terms of cost per number of preterm pre-eclampsia avoided from the initiation of aspirin or placebo 1 months after the delivery.
16. Occupation, level of income and level of education will be recorded to test the impact of socioeconomic characteristics on the cost of care and efficiency.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

Cedex 9, 2 Rue Viguerie 2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Caroline PEYROT

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Caroline PEYROT

Locations

1 EU/EEA country · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications