Efficacy of Progesterone and Low Molecular Weight Heparin in Recurrent Miscarriages (PREMISE)

September 3, 2026 updated by: Zdenek Lastuvka, General University Hospital, Prague

Randomized Open-Label Controlled Trial Evaluating the Efficacy of the Combination of Progesterone and Low Molecular Weight Heparin in Recurrent Pregnancy Loss

The objective of the trial is to assess whether the combination of enoxaparine (LMWH) with progesterone increases the live birth rate compared to standard of care (no active treatment) in women with unexplained recurrent pregnancy loss.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

264

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Czechia
      • Prague, Czechia, 12800
        • General University Hospital in Prague
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • History of ≥2 consecutive unexplained miscarriages before 20 weeks of gestation.
  • Confirmed intrauterine pregnancy by ultrasound and/or serum β-hCG (≥5 weeks).
  • Willingness to follow study procedures (progesterone use, possible daily - injections) and provide written informed consent.
  • No medical contraindication to progesterone or LMWH.

Exclusion Criteria:

  • Documented antiphospholipid syndrome or any current anticoagulant requirement.
  • Anatomical abnormalities (e.g., significant uterine malformations, large fibroids) conclusively linked to RPL.
  • Known hypersensitivity to enoxaparine or heparins, or prior heparin-induced thrombocytopenia (HIT).
  • Use of systemic steroids (beyond standard pregnancy doses) for other immunological or inflammatory conditions.
  • Severe renal insufficiency (eGFR <30 mL/min), advanced liver disease, or other clinically significant systemic autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) that may affect pregnancy or study compliance.
  • Inability or unwillingness to comply with study requirements (language barriers, severe psychiatric conditions, etc.).
  • Abnormal karyotype

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: ARM A
standard care with no active treatment
Experimental: ARM B
Intervention Arm (Progesterone + Enoxaparine)
Drug: Vaginal micronized progesterone
Vaginal micronized progesterone 800 mg daily administered in two divided doses .
Drug: Enoxaparin (LMWH)
Administered subcutaneously once daily at a weight-adjusted prophylactic dose according to body weight or applicable local guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Live Birth Rate
Time Frame: At delivery (≥24+0 weeks of gestation)
Proportion of randomized participants who deliver at least one live-born infant at ≥24+0 weeks of gestation.
At delivery (≥24+0 weeks of gestation)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing Pregnancy Rate at 22 Weeks
Time Frame: From enrollment to the end of 22 weeks of the index pregnancy.
Proportion of randomized participants with an ongoing intrauterine pregnancy at 22+0 weeks of gestation, confirmed by ultrasound demonstrating fetal cardiac activity.
From enrollment to the end of 22 weeks of the index pregnancy.
Maternal Complications
Time Frame: From enrollment to the end of treatment at 6 weeks post-labor.
Incidence of pregnancy-related complications, including preeclampsia (defined by ISSHP), gestational hypertension, gestational diabetes, placental abruption, postpartum hemorrhage (defined as estimated blood loss >500 mL following vaginal delivery or >1000 mL following cesarean section).
From enrollment to the end of treatment at 6 weeks post-labor.
Neonatal Outcomes:
Time Frame: From enrollment to the end of treatment at 6 weeks post-labor.
Birth weight (grams), APGAR scores at 1 and 5 minutes post-delivery (APGAR at 10 minutes may be recorded if available), admission to neonatal care unit (NICU), and presence of congenital anomalies confirmed postnatally.
From enrollment to the end of treatment at 6 weeks post-labor.
Safety of the trial medication
Time Frame: From enrollment to the end of treatment at 6 weeks post-labor.
Incidence of major bleeding events (overt bleeding requiring transfusion, surgical intervention, or hemodynamic intervention) and minor bleeding events (mucosal or injection-site bleeding), thrombocytopenia (defined as platelet count <100,000/μL), hypersensivity, and injection-site reactions.
From enrollment to the end of treatment at 6 weeks post-labor.
Adherence and Tolerability:
Time Frame: Treatment discontinuation: from initiation at 5-7 weeks' gestation to 36+0 weeks or delivery. Pain and missed-dose outcomes: assessed at 20 and 34 weeks' gestation and 6 weeks postpartum.
Treatment discontinuation rate and reasons for discontinuation (including adverse events); participant-reported injection-site pain associated with LMWH treatment, assessed using a numerical rating scale from 0 (no pain) to 10 (worst imaginable pain); participant-reported missed doses of study treatment and reasons for missed doses; and completeness of medication diaries.
Treatment discontinuation: from initiation at 5-7 weeks' gestation to 36+0 weeks or delivery. Pain and missed-dose outcomes: assessed at 20 and 34 weeks' gestation and 6 weeks postpartum.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

General University Hospital, Prague

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2026

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

April 24, 2026

First Submitted That Met QC Criteria

August 26, 2026

First Posted (Actual)

September 1, 2026

Study Record Updates

Last Update Posted (Actual)

September 9, 2026

Last Update Submitted That Met QC Criteria

September 3, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PREMISE LMWH-RPL_Protocol_V1.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

GDPR requirements

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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