Hydroxychloroquine in Unexplained Recurrent Pregnancy Loss

NCT05237843 | Unknown Phase 1

• 1 other identifier: HCQ in URPL
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

To investigate efficacy and safety of Hydroxychloroquin in improving pregnancy outcome in women with unexplained recurrent pregnancy loss .

Conditions

Recurrent Pregnancy Loss

Outcome Measures

Primary Outcomes (1)

• To investigate HCQ as a new edition in URPL protocol in change rate of pregnancy loss side by side with anticoagulant traditional treatment

  Describing 200 mg of HCQ daily in unexplained recurrent pregnancy loss start once she makes sure of pregnancy till 20 weeks of pregnancy

  one year to be completed

Study Arms (3)

Group A (control group)

PLACEBO COMPARATOR

35 women in this group will receive only the standard treatment in the form of : * low- dose aspirin (LDA) 81 mg/day orally (Jusprin® 81mg which manufactured by Future Pharmaceutical Company), * LMWH (Enoxaparin, Clexane® which manufactured by SANOFI company) with a dose ( .5 mg/kg) subcutaneously injected/24 hr . LDA ought to be begun before origination, while LMWH ought to be begun after confirmation of pregnancy by detecting fetal viability by ultrasound till age of viability (20wks) -PLUS Placebo specially manufactured tablets in Ain shams faculty of pharmacy will start once known she is pregnan

Drug: Hydroxychloroquine

Group B ( Hydroxychloroquine group )

EXPERIMENTAL

This group included 35 women who will administered Hydroxychloroquine 200 mg (Hydroquine® 200mg which fabricated by MinaPharm Company) one tablets / day once known she is pregnant in addition to the standard therapy (LMWH + LDA )

Drug: Hydroxychloroquine

Study Director

NO INTERVENTION

Only those directing the study know the treatment that each participant receives Placebo OR Hydroxychloroquin

Interventions

Hydroxychloroquine DRUG

Besides anti-thrombotic effects, hydroxychloroquine have immunoregulatory properties and can block the production of pro-inflammatory cytokines ( Mekinian A et al ,2015 ) , Few in vitro studies showed a potential benefit of hydroxychloroquine in early trophoblastic migration and implantation. Hydroxychloroquine restored trophoblastic fusion and differentiation and restored the annexin A5 expression.( Guller S et al ,2011 )

Also known as: placebo - Aspirin (LDA) - Clexan (LMWH)

Group A (control group); Group B ( Hydroxychloroquine group )

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: study will go on pregnant females
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged between 18 and 35 years inclusive.
• Women with at least three previous consecutive miscarriages in the first trimester of pregnancy of unknown origin with no uterine cavity abnormality that might explain recurrent miscarriage at 3D ultrasonography
• Women who have given their informed consent.
• Patient who did received standard treatment and failed in an ongoing pregnancy

You may not qualify if:

• Previous history VTE (venous thromboembolization)
• Persistent positive APL antibodies: lupus anticoagulant and/or APL (anticardiolipin or anticardiolipin IgG or IgM) titers \>99th percentile or \>40 with at least 12 weeks interval between two positive determinations (persistent antibodies) or a specific clinical setting of APS (thrombotic or obstetrical, apart from RM in the first trimester of pregnancy) .
• Known contraindication to a treatment by HCQ (retinopathy, hypersensitivity to chloroquine or HCQ, G6PD deficiency, acute intermittent porphyria, chronic liver or kidney insufficiency, extensive cutaneous psoriasis not controlled by local treatment, significant chronic digestive or haematologic disease) .
• Indication to a treatment by HCQ (rheumatoid arthritis, Lupus, solar eczema) or previous exposure for \>5years to HCQ.
• BMI \> 35
• Condition may have an effect on immune reaction e.g. history of HCV or HBV .
• Endocrinopathies such as ( DM ,thyroid disorders , hyperprolactinemia ) .
• History of hormonal contraception or intrauterine device usage in last 3 months preceeding .

Sponsors & Collaborators

• Ain Shams University: lead

Related Publications (14)

• Alijotas-Reig J, Garrido-Gimenez C. Current concepts and new trends in the diagnosis and management of recurrent miscarriage. Obstet Gynecol Surv. 2013 Jun;68(6):445-66. doi: 10.1097/OGX.0b013e31828aca19.

  PMID: 23942472 RESULT

• de Jong PG, Kaandorp S, Di Nisio M, Goddijn M, Middeldorp S. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev. 2014 Jul 4;2014(7):CD004734. doi: 10.1002/14651858.CD004734.pub4.

  PMID: 24995856 RESULT

• Sperber K, Hom C, Chao CP, Shapiro D, Ash J. Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases. Pediatr Rheumatol Online J. 2009 May 13;7:9. doi: 10.1186/1546-0096-7-9.

  PMID: 19439078 RESULT

• Garrido-Gimenez C, Alijotas-Reig J. Recurrent miscarriage: causes, evaluation and management. Postgrad Med J. 2015 Mar;91(1073):151-62. doi: 10.1136/postgradmedj-2014-132672. Epub 2015 Feb 13.

  PMID: 25681385 RESULT

• Duckitt K, Qureshi A. Recurrent miscarriage. BMJ Clin Evid. 2011 Feb 1;2011:1409.

  PMID: 21718553 RESULT

• Alijotas-Reig J, Llurba E, Gris JM. Potentiating maternal immune tolerance in pregnancy: a new challenging role for regulatory T cells. Placenta. 2014 Apr;35(4):241-8. doi: 10.1016/j.placenta.2014.02.004. Epub 2014 Feb 14.

  PMID: 24581729 RESULT

• Liang PY, Diao LH, Huang CY, Lian RC, Chen X, Li GG, Zhao J, Li YY, He XB, Zeng Y. The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure. Reprod Biomed Online. 2015 Dec;31(6):823-6. doi: 10.1016/j.rbmo.2015.08.009. Epub 2015 Aug 21.

  PMID: 26371706 RESULT

• Lim KJ, Odukoya OA, Ajjan RA, Li TC, Weetman AP, Cooke ID. The role of T-helper cytokines in human reproduction. Fertil Steril. 2000 Jan;73(1):136-42. doi: 10.1016/s0015-0282(99)00457-4.

  PMID: 10632428 RESULT

• Otun HA, Lash GE, Innes BA, Bulmer JN, Naruse K, Hannon T, Searle RF, Robson SC. Effect of tumour necrosis factor-alpha in combination with interferon-gamma on first trimester extravillous trophoblast invasion. J Reprod Immunol. 2011 Jan;88(1):1-11. doi: 10.1016/j.jri.2010.10.003. Epub 2010 Nov 26.

  PMID: 21112094 RESULT

• Haddad EK, Duclos AJ, Antecka E, Lapp WS, Baines MG. Role of interferon-gamma in the priming of decidual macrophages for nitric oxide production and early pregnancy loss. Cell Immunol. 1997 Oct 10;181(1):68-75. doi: 10.1006/cimm.1997.1199.

  PMID: 9344498 RESULT

• Onishi A, St Ange K, Dordick JS, Linhardt RJ. Heparin and anticoagulation. Front Biosci (Landmark Ed). 2016 Jun 1;21(7):1372-92. doi: 10.2741/4462.

  PMID: 27100512 RESULT

• Quaranta M, Erez O, Mastrolia SA, Koifman A, Leron E, Eshkoli T, Mazor M, Holcberg G. The physiologic and therapeutic role of heparin in implantation and placentation. PeerJ. 2015 Jan 6;3:e691. doi: 10.7717/peerj.691. eCollection 2015.

  PMID: 25653897 RESULT

• Wu XX, Guller S, Rand JH. Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression. Am J Obstet Gynecol. 2011 Dec;205(6):576.e7-14. doi: 10.1016/j.ajog.2011.06.064. Epub 2011 Jun 24.

  PMID: 21871597 RESULT

• Osadchy A, Ratnapalan T, Koren G. Ocular toxicity in children exposed in utero to antimalarial drugs: review of the literature. J Rheumatol. 2011 Dec;38(12):2504-8. doi: 10.3899/jrheum.110686. Epub 2011 Oct 15.

  PMID: 22002012 RESULT

MeSH Terms

Interventions

Hydroxychloroquine; Heparin, Low-Molecular-Weight

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Each 70 sequential patient numbers were composed murky envelope while task code composed different paper that then fixed inside. At hour predisposition visit individual control opened envelope to uncover task, continued like manner (bunch A or B ).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Group A (control group) : 35 women in this group will receive only the standard treatment in the form of low- dose aspirin (LDA) 81 mg/day (Jusprin® 81mg which manufactured by Future Pharmaceutical Company), and LMWH (Enoxaparin, Clexane® which manufactured by SANOFI company) with a dose ( .5 mg/kg) subcutaneously injected/24 hr . LDA ought to be begun before origination, while LMWH ought to be begun after confirmation of pregnancy by detecting fetal viability by ultrasound plus Placebo specially manufactured tablets in our Ain shams faculty of pharmacy . Group B ( Hydroxychloroquine group ) : This group included 35 women who will administered Hydroxychloroquine 200 mg (Hydroquine® 200mg which fabricated by MinaPharm Company) one tablets / day in addition to the standard therapy

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: February 14, 2022
• Study Start: March 1, 2022
• Primary Completion: November 1, 2022
• Study Completion: January 1, 2023
• Last Updated: February 14, 2022

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Basline
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact: yasmineabdoud@gmail.com