Pregnancy Outcomes in Women With Unexplained Recurrent Pregnancy Loss Treated With Low Dose Aspirin and Unfractionated Heparin

Objective To determine maternal and fetal outcomes in women with Unexplained RPL managed with aspirin or unfractionated heparin (UFH) plus aspirin during pregnancy.

Design: prospective clinical controlled study. Setting: high-risk pregnancy unit- Benha university hospital. Methods: Pregnant women with unexplained recurrent miscarriage attending high-risk pregnancy unit. 200 selected patients with previous unexplained recurrent miscarriage are divided into 2 groups: group A (n = 100) receive low-dose aspirin (81 mg once daily orally) plus heparin (5000 IU) every 12 h with the first positive pregnancy test while group B (n = 100) receive no thing .

Main outcome measures: Maternal outcomes included thromboembolic and haemorrhagic complications and pregnancy-induced hypertension .Prematurity, intrauterine growth restriction and neonatal death were considered as maternal and fetal complications

Study Overview

• Status: Recruiting
• Conditions: Recurrent Pregnancy Loss
• Intervention / Treatment: Drug: Heparin

Detailed Description

This prospective comparative, controlled clinical study is conducted at Department of Obstetrics and Gynecology, Benha University Hospital, and a private center, from June 2012 . After approval of the study protocol by the Local Ethical Committee and obtaining written fully informed patients' consents. All patients are interviewed about their medical, personal, family, obstetrical and thrombosis history. All patients included in study complain of three or more unexplained consecutive spontaneous abortions.

All patients (n=200) are in good general health without previous history of Diabetes Mellitus or thyroid dysfunction or cardiac disease. Patients with Thrombocytopenia (<100000/ml), bleeding tendencies, ectopic pregnancy, past history of vascular thrombosis ,uterine anomalies and multiple gestation are excluded from the study.

complete blood picture, urine routine examination, blood sugar, blood grouping, Bleeding Time, Clotting Time, Prothrombin Time, Activated Partial Thromboplastin Time, Hepatitis B Surface Ag, Hepatitis C Virus screening are offered to all patients and findings noted as soon as they conceived. All patients are given routine Folic Acid, Iron and Calcium supplementation orally daily during antenatal period (whether conceived spontaneously or with treatment

200 selected patients with previous unexplained recurrent pregnancy loss are divided into 2 groups:Group A (n = 100) are put on Inj. UFH (Cal-heparin) 5000 U subcutaneous twice daily plus Aspirin 81 mg/day (Juspirin) with the first positive pregnancy test, Inj. UFH is given either into anterior abdominal wall or anterior aspect of thigh subcutaneously. While group B (n = 100) receive no thing

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • El Qualyobia
    • Banhā, El Qualyobia, Egypt, 13518
      • Recruiting
      • Benha univesity hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 46 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• patients with unexplained recurrent pregnancy loss (RPL)

Exclusion Criteria:

• previous history of Diabetes Mellitus or thyroid dysfunction or cardiac disease
• Thrombocytopenia (<100000/ml)
• bleeding tendencies
• ectopic pregnancy
• past history of vascular thrombosis
• uterine anomalies
• multiple gestation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A(heparin group); Group A (n = 100) are put on Inj. UFH (Cal-heparin) 5000 U subcutaneous twice daily plusAspirin 81 mg/day (Juspirin) with the first positive pregnancy test, Inj. UFH is given either into anterior abdominal wall or anterior aspect of thigh subcutaneously	Drug: Heparin; Group A (n = 100) are put on Inj. UFH (Cal-heparin) 5000 U subcutaneous twice daily plusAspirin 81 mg/day (Juspirin) with the first positive pregnancy test, Inj. UFH is given either into anterior abdominal wall or anterior aspect of thigh subcutaneously; Other Names: cal-heparin 5000 U; juspirin
NO_INTERVENTION: Group B; group B (n = 100) receive no thing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pregnancy loss	evidence of abortion is assessed clinically by vaginal bleeding and passage of contents of conception through vagina or by ultrasound through detecting missed abortion .	during first 20 weeks of gregnancy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal outcomes	Maternal outcomes include thromboembolic and hemorrhagic complications and pregnancy-induced hypertension.these outcomes is assessed clinically by follow up mother throughout pregnancy e.g frequent blood pressure monitoring	during 40 weeks of pregnancy
prematurity	delivery of babies before fetal maturity which necessitate admission to the neonatal unit	after 20 weeks and before 37 weeks gestation
fetal outcome	Foetal growth is monitored by fundal height measurement and serial ultrasounds. Doppler umbilical wave flow velocity is studied for foetuses with suspected intrauterine growth retardation	during last half of pregnancy(last 20 weeks)

Collaborators and Investigators

• Sponsor: Benha University
• Investigators: Principal Investigator: ahmed saad, benha faculty of medicine; Principal Investigator: Ibrahim ali, MD, Ain Shams University

Publications and helpful links

General Publications

• Hamulyak EN, Scheres LJ, Marijnen MC, Goddijn M, Middeldorp S. Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Cochrane Database Syst Rev. 2020 May 2;5(5):CD012852. doi: 10.1002/14651858.CD012852.pub2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 23, 2019
• Primary Completion (ANTICIPATED): October 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: May 16, 2014
• First Submitted That Met QC Criteria: May 19, 2014
• First Posted (ESTIMATE): May 21, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 14, 2022
• Last Update Submitted That Met QC Criteria: January 30, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Aspirin, heparin, pregnancy, recurrent pregnancy loss
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pregnancy Complications; Death; Recurrence; Abortion, Spontaneous; Abortion, Habitual; Fetal Death; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: khalid-ahmed 3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No