LDA and LMWH vs LDA Alone in High-risk Patients for Preeclampsia Prevention

NCT07361679 | Recruiting Phase 4

• 1 other identifier: 724/23-11-2022
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. Low-dose aspirin started in the first trimester reduces the risk of preeclampsia in high-risk women. Low molecular weight heparin (LMWH) has shown potential benefits in addition to aspirin for preventing preeclampsia through its anticoagulant, anti-inflammatory, and endothelial protective effects. However, current evidence is limited and conflicting regarding the added value of LMWH to aspirin. This randomized controlled trial aims to evaluate the efficacy of combined aspirin and LMWH, compared to aspirin alone, for reducing the incidence of preeclampsia in high-risk gravidas.

Conditions

Preeclampsia Severe; Toxemia Of Pregnancy; Preeclampsia; Pregnancy Complications; Hypertension, Pregnancy-Induced; Gestational Hypertension

Keywords

preeclampsia; gestational hypertension; toxemia; Preeclampsia prevention; Low molecular weight heparin; tinzaparin; High-risk pregnancy; LMWH; Maternal-fetal medicine

Outcome Measures

Primary Outcomes (1)

• Incidence of Preeclampsia

  Preeclampsia defined as gestational hypertension (BP ≥140/90 mmHg on at least two measurements ≥4 hours apart) after 20 weeks' gestation accompanied by one or more of: (1) Proteinuria (≥30 mg/mmol protein:creatinine ratio, ≥8 mg/mmol albumin:creatinine ratio, ≥0.3 g/24h, or ≥2+ dipstick); (2) Maternal end-organ dysfunction including neurological complications (severe headaches, visual scotomata, eclampsia, stroke, clonus), pulmonary oedema, haematological complications (platelet count \<150,000/μL, disseminated intravascular coagulation, haemolysis), acute kidney injury (creatinine ≥90 μmol/L or 1 mg/dL), or liver involvement (elevated ALT or AST \>40 IU/L); or (3) Uteroplacental dysfunction (fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, placental abruption, angiogenic imbalance, or intrauterine fetal death), per ISSHP 2021 classification.

  From enrollment until delivery (up to 40 weeks gestation)

Secondary Outcomes (14)

• Systemic Immune-Inflammation Index (SII)

  At 20-24 weeks, 32-34 weeks, and 36 weeks gestation

• Incidence of Preterm Preeclampsia

  From enrollment until 37 weeks gestation

• Prevalence of placental histopathological lesions

  At delivery

• Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Levels

  At 20-24 weeks, 32-34 weeks, and 36 weeks gestation

• Placental Growth Factor (PlGF) Levels

  At 20-24 weeks, 32-34 weeks, and 36 weeks gestation

Study Arms (2)

Aspirin Alone

ACTIVE COMPARATOR

Participants receive aspirin 160 mg orally once daily before bedtime from enrollment (\<16 weeks gestation) until 36 weeks gestation.

Drug: Aspirin

Aspirin plus LMWH

EXPERIMENTAL

Participants receive aspirin 160 mg orally once daily before bedtime PLUS weight-adjusted tinzaparin subcutaneously once daily in the morning (4,500 Anti-Xa IU for weight ≤60 kg, 6,000 Anti-Xa IU for weight 60-90 kg, 8,000 Anti-Xa IU for weight \>90 kg) from enrollment (\<16 weeks gestation) until 36 weeks gestation.

Drug: Aspirin; Drug: Tinzaparin

Interventions

Aspirin DRUG

Aspirin 160 mg orally once daily before bedtime. Duration: From enrollment (\<16 weeks gestation) until 36 weeks gestation.

Also known as: ASA, Low-dose aspirin, Acetylsalicylic acid

Aspirin Alone; Aspirin plus LMWH

Tinzaparin DRUG

Weight-adjusted tinzaparin administered subcutaneously once daily in the morning: 4,500 Anti-Xa IU/day for weight ≤60 kg, 6,000 Anti-Xa IU/day for weight 60-90 kg, and 8,000 Anti-Xa IU/day for weight \>90 kg. Duration: From enrollment (\<16 weeks gestation) until 36 weeks gestation.

Also known as: Low molecular weight heparin, Innohep, LMWH

Aspirin plus LMWH

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Singleton pregnancy
• High risk for preeclampsia (risk \>1:150) based on FMF screening algorithm combining first-trimester ultrasound, biochemical markers, and medical history
• Gestational age \<16 weeks at enrollment
• Maternal age ≥18 years
• Willing and able to provide written informed consent
• Adequate ability for follow-up (direct telephone communication, accessible residence)

You may not qualify if:

• Multiple pregnancy
• Current permanent aspirin use for other medical indications
• Serious congenital fetal abnormality detected on ultrasound
• Contraindication to aspirin or low molecular weight heparin including: known hypersensitivity, active peptic ulcer disease, bleeding disorders or coagulopathy, severe thrombocytopenia (platelet count \<100,000/μL), active or recent significant bleeding, history of heparin-induced thrombocytopenia
• Pre-existing severe renal failure (creatinine clearance \<30 mL/min)
• Unable to provide informed consent
• Low probability of adequate follow-up (residence in remote areas without telephone access, accommodation in temporary structures)

Sponsors & Collaborators

• Alexandra Hospital, Athens, Greece: lead

Study Sites (1)

First Department of Obstetrics and Gynecology, Alexandra Hospital

Athens, Attica, 11528, Greece

RECRUITING

Related Publications (6)

• McLaughlin K, Baczyk D, Potts A, Hladunewich M, Parker JD, Kingdom JC. Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia. Hypertension. 2017 Jan;69(1):180-188. doi: 10.1161/HYPERTENSIONAHA.116.08298. Epub 2016 Nov 13.

  PMID: 27840330 BACKGROUND

• Cruz-Lemini M, Vazquez JC, Ullmo J, Llurba E. Low-molecular-weight heparin for prevention of preeclampsia and other placenta-mediated complications: a systematic review and meta-analysis. Am J Obstet Gynecol. 2022 Feb;226(2S):S1126-S1144.e17. doi: 10.1016/j.ajog.2020.11.006. Epub 2021 Apr 20.

  PMID: 34301348 BACKGROUND

• Wright D, Wright A, Nicolaides KH. The competing risk approach for prediction of preeclampsia. Am J Obstet Gynecol. 2020 Jul;223(1):12-23.e7. doi: 10.1016/j.ajog.2019.11.1247. Epub 2019 Nov 13.

  PMID: 31733203 BACKGROUND

• Magee LA, Brown MA, Hall DR, Gupte S, Hennessy A, Karumanchi SA, Kenny LC, McCarthy F, Myers J, Poon LC, Rana S, Saito S, Staff AC, Tsigas E, von Dadelszen P. The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2022 Mar;27:148-169. doi: 10.1016/j.preghy.2021.09.008. Epub 2021 Oct 9.

  PMID: 35066406 BACKGROUND

• Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017 Aug 17;377(7):613-622. doi: 10.1056/NEJMoa1704559. Epub 2017 Jun 28.

  PMID: 28657417 BACKGROUND

• Magee LA, Nicolaides KH, von Dadelszen P. Preeclampsia. N Engl J Med. 2022 May 12;386(19):1817-1832. doi: 10.1056/NEJMra2109523. No abstract available.

  PMID: 35544388 BACKGROUND

MeSH Terms

Conditions

Pre-Eclampsia; Pregnancy Complications; Hypertension, Pregnancy-Induced; Toxemia

Interventions

Aspirin; Tinzaparin; Heparin, Low-Molecular-Weight

Condition Hierarchy (Ancestors)

Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Infections

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Georgios Daskalakis, PhD

  First Department of Obstetrics and Gynecology, Alexandra Hospital

  STUDY CHAIR

Central Study Contacts

Dimitrios Baroutis, MD, MSc, PhD(c)

CONTACT

+306978275745; dbaroutis@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Obstetrics and Gynecology

Model Details: Two parallel groups: Arm 1 receives aspirin alone, Arm 2 receives aspirin plus weight-adjusted LMWH

Study Record Dates

• First Submitted: December 21, 2025
• First Posted: January 23, 2026
• Study Start: January 18, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

GR (1)