Efficacy of Progesterone and Low Molecular Weight Heparin in Recurrent Miscarriages

NCT07796737 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: PREMISE LMWH-RPL_Protocol_V1.0
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pregnancy Loss; Pregnancy Loss, Early

Keywords

progesterone; low molecular weight heparine; recurrent miscarriage; pregnancy loss

Outcome Measures

Primary Outcomes (1)

• Live Birth Rate

  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 Outcomes (5)

• Ongoing Pregnancy Rate at 22 Weeks

  From enrollment to the end of 22 weeks of the index pregnancy.

• Maternal Complications

  From enrollment to the end of treatment at 6 weeks post-labor.

• Neonatal Outcomes:

  From enrollment to the end of treatment at 6 weeks post-labor.

• Safety of the trial medication

  From enrollment to the end of treatment at 6 weeks post-labor.

• Adherence and Tolerability:

  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.

Study Arms (2)

ARM A

NO INTERVENTION

standard care with no active treatment

ARM B

EXPERIMENTAL

Intervention Arm (Progesterone + Enoxaparine)

Drug: Vaginal micronized progesterone; Drug: Enoxaparin (LMWH)

Interventions

Vaginal micronized progesterone DRUG

Vaginal micronized progesterone 800 mg daily administered in two divided doses .

ARM B

Enoxaparin (LMWH) DRUG

Administered subcutaneously once daily at a weight-adjusted prophylactic dose according to body weight or applicable local guidelines.

ARM B

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Only pregnant patients are enrolled.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• General University Hospital, Prague: lead

Study Sites (1)

General University Hospital in Prague

Prague, 12800, Czechia

Location

Related Publications (7)

• Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Greaves M, Whyte S, Greer IA; Scottish Pregnancy Intervention Study (SPIN) collaborators. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood. 2010 May 27;115(21):4162-7. doi: 10.1182/blood-2010-01-267252. Epub 2010 Mar 17.

  PMID: 20237316 BACKGROUND

• Gris JC, Mercier E, Quere I, Lavigne-Lissalde G, Cochery-Nouvellon E, Hoffet M, Ripart-Neveu S, Tailland ML, Dauzat M, Mares P. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood. 2004 May 15;103(10):3695-9. doi: 10.1182/blood-2003-12-4250. Epub 2004 Jan 22.

  PMID: 14739212 BACKGROUND

• Coomarasamy A, Williams H, Truchanowicz E, Seed PT, Small R, Quenby S, Gupta P, Dawood F, Koot YE, Bender Atik R, Bloemenkamp KW, Brady R, Briley AL, Cavallaro R, Cheong YC, Chu JJ, Eapen A, Ewies A, Hoek A, Kaaijk EM, Koks CA, Li TC, MacLean M, Mol BW, Moore J, Ross JA, Sharpe L, Stewart J, Vaithilingam N, Farquharson RG, Kilby MD, Khalaf Y, Goddijn M, Regan L, Rai R. A Randomized Trial of Progesterone in Women with Recurrent Miscarriages. N Engl J Med. 2015 Nov 26;373(22):2141-8. doi: 10.1056/NEJMoa1504927.

  PMID: 26605928 BACKGROUND

• Ectopic pregnancy and miscarriage: diagnosis and initial management. London: National Institute for Health and Care Excellence (NICE); 2023 Aug 23. Available from http://www.ncbi.nlm.nih.gov/books/NBK544906/

  PMID: 31393678 BACKGROUND

• Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, Williams H, Eapen AK, Roberts T, Ogwulu CC, Goranitis I, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Crosfill F, Deb S, Duncan WC, Ewer A, Hinshaw K, Holland T, Izzat F, Johns J, Kriedt K, Lumsden MA, Manda P, Norman JE, Nunes N, Overton CE, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingam N, Watkins L, Wykes C, Horne A, Jurkovic D. A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. N Engl J Med. 2019 May 9;380(19):1815-1824. doi: 10.1056/NEJMoa1813730.

  PMID: 31067371 BACKGROUND

• Christiansen OB, Nybo Andersen AM, Bosch E, Daya S, Delves PJ, Hviid TV, Kutteh WH, Laird SM, Li TC, van der Ven K. Evidence-based investigations and treatments of recurrent pregnancy loss. Fertil Steril. 2005 Apr;83(4):821-39. doi: 10.1016/j.fertnstert.2004.12.018.

  PMID: 15820784 BACKGROUND

• ESHRE Guideline Group on RPL; Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Mcheik S, Peramo B, Quenby S, Nielsen HS, van der Hoorn ML, Vermeulen N, Goddijn M. ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023 Mar 2;2023(1):hoad002. doi: 10.1093/hropen/hoad002. eCollection 2023.

  PMID: 36873081 BACKGROUND

MeSH Terms

Conditions

Abortion, Spontaneous; Abortion, Habitual

Interventions

Enoxaparin; Heparin, Low-Molecular-Weight

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Central Study Contacts

Zdeněk Laštůvka, MD, PhD

CONTACT

+420 224767577; zdenek.lastuvka@vfn.cz

Jana Brabcová, PhD

CONTACT

+420 22476 7496; jana.brabcova3@vfn.cz

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: April 24, 2026
• First Posted: September 1, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: September 9, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)