Efficacy of Progesterone and Low Molecular Weight Heparin in Recurrent Miscarriages (PREMISE)
3. september 2026 oppdatert av: 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.
Studieoversikt
Status
Har ikke rekruttert ennå
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Antatt)
264
Fase
- Fase 3
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiekontakt
- Navn: Zdeněk Laštůvka, MD, PhD
- Telefonnummer: +420 224767577
- E-post: zdenek.lastuvka@vfn.cz
Studer Kontakt Backup
- Navn: Jana Brabcová, PhD
- Telefonnummer: +420 22476 7496
- E-post: jana.brabcova3@vfn.cz
Studiesteder
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-
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Prague, Tsjekkia, 12800
- General University Hospital in Prague
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Ta kontakt med:
- Zdeněk Laštůvka, MD, PhD
- Telefonnummer: +420 224 76 7577
- E-post: zdenek.lastuvka@gmail.com
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-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
Tar imot friske frivillige
Nei
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Ingen inngripen: ARM A
standard care with no active treatment
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Eksperimentell: ARM B
Intervention Arm (Progesterone + Enoxaparine)
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Vaginal micronized progesterone 800 mg daily administered in two divided doses .
Administered subcutaneously once daily at a weight-adjusted prophylactic dose according to body weight or applicable local guidelines.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Live Birth Rate
Tidsramme: At delivery (≥24+0 weeks of gestation)
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Proportion of randomized participants who deliver at least one live-born infant at ≥24+0 weeks of gestation.
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At delivery (≥24+0 weeks of gestation)
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Ongoing Pregnancy Rate at 22 Weeks
Tidsramme: From enrollment to the end of 22 weeks of the index pregnancy.
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Proportion of randomized participants with an ongoing intrauterine pregnancy at 22+0 weeks of gestation, confirmed by ultrasound demonstrating fetal cardiac activity.
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From enrollment to the end of 22 weeks of the index pregnancy.
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Maternal Complications
Tidsramme: From enrollment to the end of treatment at 6 weeks post-labor.
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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).
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From enrollment to the end of treatment at 6 weeks post-labor.
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Neonatal Outcomes:
Tidsramme: From enrollment to the end of treatment at 6 weeks post-labor.
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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.
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From enrollment to the end of treatment at 6 weeks post-labor.
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Safety of the trial medication
Tidsramme: From enrollment to the end of treatment at 6 weeks post-labor.
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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.
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From enrollment to the end of treatment at 6 weeks post-labor.
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Adherence and Tolerability:
Tidsramme: 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.
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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.
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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.
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
- 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.
- 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/
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Antatt)
1. desember 2026
Primær fullføring (Antatt)
31. desember 2029
Studiet fullført (Antatt)
31. desember 2030
Datoer for studieregistrering
Først innsendt
24. april 2026
Først innsendt som oppfylte QC-kriteriene
26. august 2026
Først lagt ut (Faktiske)
1. september 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
9. september 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
3. september 2026
Sist bekreftet
1. september 2026
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- PREMISE LMWH-RPL_Protocol_V1.0
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
IPD-planbeskrivelse
GDPR requirements
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
produkt produsert i og eksportert fra USA
Nei
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