CHASAP : Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy, a multicenter prospective randomized double-blind placebo-controlled trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Intercommunal Creteil

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

27 Jan 2021 → ongoing

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DGOS

External identifiers

EU CT number

2024-516461-36-00

EudraCT number

2018-004160-58

ClinicalTrials.gov

NCT04356326

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To compare, in pregnant women with chronic hypertension, the efficacy of Aspirin (acetylsalicylic acid) at a dose of 150 mg / day with a placebo, in the prevention of maternal-fetal morbidity and mortality (preeclampsia, placental abruption, IUGR, perinatal death, maternal death, and preterm delivery).

Secondary objectives 7

1. To compare the preventive effect of low-dose aspirin in the prevention of maternal-fetal morbidity and mortality according to the term of beginning of the treatment: before or after 15 SA
2. To estimate this preventive effect on each of the events of the main composite criterion individually. Concerning the rate of superimposed PE, it will be analyzing according the two definition specified in the rational od the study,
3. To estimate this preventive effect on each of the following: the severity of PE, IUGR, and preterm delivery; the risks of miscarriage, fetal death, neonatal death; the neonatal morbidity (stay in neonatal intensive care unit, assisted ventilation > 24 hours, hyaline membrane disease, stage III or IV intraventricular hemorrhage),
4. To evaluate the potential toxicity of the active treatment: major maternal hemorrhagic event (externalized active bleeding, intracranial, intraocular, retroperitoneal, or articular bleeding), or minor,
5. To analyze patients' adherence with treatment (logbook)
6. To analyze the efficacy of treatment in the group of aspirin responders (thromboxane B2 assay)
7. The constitution of a biological collection associated with maternal and perinatal clinical data: Complete evaluation of the circulating angiogenic profile by systematic assay of free and bound fractions of pro and antiangiogenic factors (PlGF, sFlt-1, sEng)

Conditions and MedDRA coding

Pregnancy associated hypertension, Pre-Eclampsia, Fetal growth restriction

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Pregnant women between 10 weeks and 19 weeks + 6 days
2. Chronic hypertension, whether treated or not
3. ­Singleton pregnancy
4. Signed the written informed consent
5. Affiliation to social security

Exclusion criteria 21

1. Medical history requiring anticoagulation (antiphospholipid syndrome, deep vein thromboembolic disease, pulmonary embolism, atherothrombosis, patient with mechanical heart valves),
2. Patient receiving aspirin for another indication outside pregnancy
3. Patient with significant proteinuria (> 300mg/24 hours or a proteinuria/creatininuria ratio ≥ 30mg/mmol),
4. Active bleeding,
5. History of severe PE with delivery < 34 weeks of gestation,
6. Hypersensitivity to salicylates such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)
7. Platelet count lower than 100,000 cells/microliter (dosage less than 6 months old),
8. Hemostasis disorders, including hemophilia (with thrombocytopenia)
9. Any constitutional or acquired hemorrhagic disease, (including digestive haemorrhages, history of haemorrhagic stroke and thrombocytopenia
10. Human immunodeficiency virus, or hepatitis B virus, or hepatitis C virus positive serum,
11. Patient included in another interventional study which could interfere with the results of the study
12. Age <18 years old,
13. Geographic inaccessibility (less likely to comply with necessary follow-up visits and Care),
14. Women under the protection of justice,
15. Patients with psychiatric follow-up, poor understanding of French or cognitive problems.
16. Duodenal ulcer,
17. Severe renal impairment,
18. Severe hepatic insufficiency,
19. Severe cardiac impairment
20. Gout
21. Patients with known glucose-6-phosphate dehydrogenase deficiency,

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. It is a composite morbidity-mortality criterion comprising at least one of the following: ­ Preeclampsia (early or late) ­ Birthweight <10 percentile ­ Placental abruption ­ Perinatal death ­ Maternal death ­ Preterm delivery < 37 weeks of gestation

Secondary endpoints 14

1. Rate of the composite morbidity-mortality criterion in 2 subgroups: treatment started before or after 15 SA
2. Each of the events of primary end-point taken individually,
3. Rate of severe PE
4. Rate of severe IUGR (< 5th percentile of birth weight),
5. Rate of severe preterm delivery (< 34 weeks of gestation),
6. Rate of fetal loss (fetal loss between 10 and 21 weeks of gestation),
7. Rate of fetal death (fetal death from 22 weeks of gestation until delivery),
8. Rate of neonatal death (death from birth until 28 days),
9. Neonatal morbidity  stay in a neonatal intensive care unit,  assisted ventilation > 24 hours,  hyaline membrane disease,  intraventricular hemorrhages stage III or IV,
10. Potential toxicity of the treatment: major maternal bleeding event (active externalized, intracranial, intra-ocular, retroperitoneal, articular), or minor
11. Adherence of treatment (diary) and its relationship with the efficacy of the preventive effect on primary outcome,
12. Biological response to the treatment (response to the treatment will be defined as a serum thromboxane B2 > 10ng/mL)
13. Circulating and urinary angiogenic profile associated with maternal and fetal clinical data: sFLT1 (serum and urine), PlGF (serum and urine)
14. Child psychomotor development and health problems at 2 and 4 years of age

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Intercommunal Creteil

Sponsor organisation

Centre Hospitalier Intercommunal Creteil

Address

40 Avenue De Verdun

City

Creteil

Postcode

94000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

Edouard LECARPENTIER

Public contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

DRSI CHIC

Locations

1 EU/EEA country · 17 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 10 files

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

Application history

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