Pregnancy Related, Protein S Deficiency
Conditions
Keywords
Protein S Deficiency, pregnancy, therapy
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.
Interventions
DRUGEnoxaparin
Enoxaparin 4000 IU/day by subcutaneous injection at the time of randomization and continued until delivery. Dose adjustments were made throughout the study based on symptoms such as bleeding and thrombosis.
DRUGAspirin
Aspirin 75mg, orally, once daily at the time of randomization and continued until delivery. Dose adjustments were made throughout the study based on symptoms such as bleeding and thrombosis.
Sponsors
Beijing Obstetrics and Gynecology Hospital
Beijing Hospital
Peking Union Medical College Hospital
China-Japan Friendship Hospital
Sichuan Academy of Medical Sciences
Xiangya Hospital of Central South University
Chinese PLA General Hospital
Beijing Friendship Hospital
Beijing Chuiyangliu Hospital
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of livebirth | From date of randomization until delivery, assessed up to 42 months | Incidents of livebirth |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidents of placental insufficiency | up to 6 weeks post-partum | Incidents of pre-eclampsia, intrauterine growth retardation, placental abruption, and intrauterine foetal death, etc. |
| 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 % |
| 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 |
| 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) |
| Incidents of thrombosis/thromboembolism | From the start of study treatment to 6 weeks post-partum | thrombosis/thromboembolism |
| 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 |
Countries
China
Contacts
Primary ContactXiao-Hui Zhang, Professor
Backup ContactMeng-Tong Zang, MD
Outcome results
None listed