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

Peking University

Status and phase: Not yet enrolling; Phase 2

Conditions: Pregnancy Related; Protein S Deficiency

Treatments: Drug: Aspirin; Drug: Enoxaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT06531525

PKU-PS-01

Details and patient eligibility

About

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

Full 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.

Enrollment: 48 estimated patients

Sex: Female

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 4 patient groups

The combination group

Experimental group

Description:

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.

Treatment:

Drug: Enoxaparin

Drug: Aspirin

Drug: Enoxaparin

The Aspirin group

Active Comparator group

Description:

Aspirin will be given at a dose of 75mg, orally, each day until delivery.

Treatment:

Drug: Aspirin

No intervention

No Intervention group

Description:

No intervention

All groups

Other group

Description:

Participants in all groups will receive daily injections of enoxaparin at a dose of 4000 IU within 6 weeks at postpartum.

Treatment:

Drug: Enoxaparin

Drug: Enoxaparin