Clinical trial NCT06531525: Effect of Low Molecular Heparin on Pregnancy Outcome With Protein S Deficiency
Official title: A Multicenter, Open-label, Randomized, Controlled, Phase 2 Trial Evaluating Whether Low Molecular Heparin Could Improve Pregnancy Outcomes With Protein S Deficiency
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Pregnancy Related
Protein S Deficiency
Keywords: Protein S Deficiency
pregnancy
therapy
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Obstetrics and Gynecology Hospital
name: Beijing Hospital
name: Peking Union Medical College Hospital
name: China-Japan Friendship Hospital
name: Sichuan Academy of Medical Sciences
name: Xiangya Hospital of Central South University
name: Chinese PLA General Hospital
name: Beijing Friendship Hospital
name: Beijing Chuiyangliu Hospital
First posted: 2024-08-01
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of livebirth
timeFrame: From date of randomization until delivery, assessed up to 42 months
Secondary outcomes:
measure: Parameters of maternal coagulation-related indicators
timeFrame: From the start of study treatment to 6 weeks post-partum
measure: Parameters to assess the safety of low molecular heparin
timeFrame: From the start of study treatment to 6 weeks post-partum
measure: Other incidents of adverse pregnancy outcomes
timeFrame: up to 37 weeks
measure: Neonatal Data
timeFrame: after the delivery (an expected average of one month)
measure: Incidents of placental insufficiency
timeFrame: up to 6 weeks post-partum
measure: Incidents of thrombosis/thromboembolism
timeFrame: From the start of study treatment to 6 weeks post-partum
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Insititute of Hematology, Peking University People's Hospital
state: Beijing/Beijing
Study officials:
affiliation: Peking University Insititute of Hematology, Peking University People's Hospital
name: Xiao-Hui Zhang, Professor
role: PRINCIPAL_INVESTIGATOR
References: