Effect of Low Molecular Heparin on Pregnancy Outcome With Protein S Deficiency

Phase 2

Not yet recruiting

• Conditions: Pregnancy Related; Protein S Deficiency
• Interventions: Drug: Enoxaparin; Drug: Aspirin

• Registration Number: NCT06531525
• Lead Sponsor: Peking University People's Hospital

Brief Summary

To evaluate whether low molecular heparin could improve pregnancy outcomes in pregnancies with protein S deficiency.

Detailed Description

This is a parallel-group, multicenter, randomized controlled trial of 48 pregnancies with protein S deficiency in China. Patients are randomized into three groups to receive enoxaparin combined with aspirin, aspirin alone and no intervention. The primary outcome measure is livebirth rate.

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-22
• Study First Submitted QC: 2024-07-29
• Last Update Submitted: 2024-07-29
• Study Start: 2024-08-01
• Study First Posted: 2024-08-01
• Last Update Posted: 2024-08-01
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 48

Inclusion Criteria

1. Plasma activity levels of PS when not pregnant are below the lower limits of the adult reference values (generally about 60-70% for PS) without the use of warfarin. Or, free protein S antigen levels in the second and third trimesters are less than 30% and less than 24%, respectively
2. Pregnant women who delivered from Aug 1st, 2024 to Oct 15th, 2027
3. One or more family members exhibiting the same symptoms as the patient
4. Past history of early onset thrombosis (age 50 or below)
5. Repeated recurrence of thrombosis
6. Thromboses in unusual sites
7. New onset of thrombosis during current pregnancy or after delivery
8. Patients with diagnosis confirmed by gene analysis Inclusion criteria 1 and 2 must always be met regardless of items of 3-8.
9. Written informed consent

Exclusion Criteria

1. Thrombophilia other than Protein S deficiency
2. Antiphospholipid syndrome, systemic lupus erythematosus, platelet abnormalities, vascular disorders, blood flow obstruction, paroxysmal nocturnal hemoglobinuria, malignant tumor and other conditions that tend to cause thrombosis
3. Allergy/hypersensitivity to enoxaparin or aspirin
4. Heparin-associated thrombocytopenia or thrombocytopenia (platelet count<75 × 10^9/L)
5. Organ lesions at risk for bleeding such as acute stomach/bowel ulcers, cerebral hemorrhage, cerebral aneurysm
6. uncontrolled hypertension or Severe hypertension (Systolic Blood Pressure >200mmhg and/or Diastolic Blood Pressure >120mmHg)
7. Severe hepatic failure (INR >1.8)
8. Serum creatinine greater than 80 umol/L (1.3mg/dl) and an abnormal 24 hour urine creatine clearance (<30ml/min)
9. Abnormal uterine cavity on hysterosalpingogram/hysteroscopy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
All groups	Enoxaparin	Participants in all groups will receive daily injections of enoxaparin at a dose of 4000 IU within 6 weeks at postpartum.
The combination group	Enoxaparin	Subjects randomized to the combination group will receive daily injections of enoxaparin at a dose of 4000 IU and aspirin 75mg per day orally until delivery.
The combination group	Aspirin	Subjects randomized to the combination group will receive daily injections of enoxaparin at a dose of 4000 IU and aspirin 75mg per day orally until delivery.
The Aspirin group	Aspirin	Aspirin will be given at a dose of 75mg, orally, each day until delivery.

Primary Outcome Measures

Name	Time	Method
Rate of livebirth	From date of randomization until delivery, assessed up to 42 months	Incidents of livebirth

Secondary Outcome Measures

Name	Time	Method
Parameters of maternal coagulation-related indicators	From the start of study treatment to 6 weeks post-partum	D-Dimer in ng/ml, Protein S activity in %
Incidents of placental insufficiency	up to 6 weeks post-partum	Incidents of pre-eclampsia, intrauterine growth retardation, placental abruption, and intrauterine foetal death, etc.
Other incidents of adverse pregnancy outcomes	up to 37 weeks	early miscarriage (until 12 weeks of gestation), late miscarriage (12-28 weeks of gestation), premature livebirths (28-37 weeks of gestation)
Neonatal Data	after the delivery (an expected average of one month)	Neonatal weight in grams, Neonatal length in centimetres, Apgar 1-minute, 5-minute, 10-minute scores in scores, Number of neonatal complications
Parameters to assess the safety of low molecular heparin	From the start of study treatment to 6 weeks post-partum	Maternal platelet count in 10\^9/L, Number of haemorrhagic events, Number of cases of skin reactions at injection site
Incidents of thrombosis/thromboembolism	From the start of study treatment to 6 weeks post-partum	thrombosis/thromboembolism

Trial Locations

Locations (1)

Peking University Insititute of Hematology, Peking University People's Hospital; 🇨🇳 Beijing, Beijing/Beijing, China