Low Dose Prednisone Therapy in Women With Recurrent Pregnancy Loss

NCT04558268 | Unknown Phase 2

• 1 other identifier: SOR-0461-18-CTIL
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

Brief Summary

For many years there is a lack of large randomized controlled trials that study the effect of low dose prednisone in women with RPL and thus the evidence of a probable efficacy of prednisone in RPL women remains limited and unclear. As the ESHRE recommended in 2018 (2) we aim to assess the effect of such treatment in a large trial that includes unexplained and abnormal autoimmune profile RPL patients. we also aim to assess the side effects of the treatment in RPL pregnant women.

Conditions

Recurrent Pregnancy Loss(RPL); Recurrent Miscarriage

Keywords

Recurrent pregnancy loss(RPL); Recurrent miscarriage; Prednisone; Autoimmune antibodies; Life birth rate

Outcome Measures

Primary Outcomes (2)

• Live birth

  birth that occurs after 24 weeks of gestation.

  through study completion, an average of 1 year.

• Pregnancy loss

  birth that occurs up to 24 weeks of gestation.

  through study completion, an average of 1 year.

Study Arms (2)

treatment group

EXPERIMENTAL

Drug: Prednisone; Drug: Progesterone; Dietary Supplement: vit D; Dietary Supplement: Iron Supplement; Dietary Supplement: Folic Acid

placebo group

PLACEBO COMPARATOR

Drug: Progesterone; Dietary Supplement: vit D; Dietary Supplement: Iron Supplement; Dietary Supplement: Folic Acid

Interventions

Prednisone DRUG

Prednisone is a corticosteroid. It prevents the release of substances in the body that cause inflammation. It also suppresses the immune system. Prednisone is used as an anti-inflammatory or an immunosuppressant medication. Prednisone treats many different conditions such as allergic disorders, skin conditions, ulcerative colitis, arthritis, lupus, psoriasis, or breathing disorders.

treatment group

Progesterone DRUG

Progesterone is a female hormone important for the regulation of ovulation and menstruation. Progesterone is used to cause menstrual periods in women who have not yet reached menopause but are not having periods due to a lack of progesterone in the body. It is also used to prevent overgrowth in the lining of the uterus in postmenopausal women who are receiving estrogen hormone replacement therapy.

placebo group; treatment group

vit D DIETARY_SUPPLEMENT

Vitamin D acts on our bones, intestines, kidneys and parathyroid glands to keep calcium in balance throughout our body. Vitamin D receptors are also located within our cardiovascular system, lungs, pancreas, skeletal muscle, skin, and reproductive organs. In summary, vitamin D is a prohormone that is essential for good health.

placebo group; treatment group

Iron Supplement DIETARY_SUPPLEMENT

Iron is one of the minerals in the human body. It is one of the components of hemoglobin, the substance in red blood cells that helps blood carry oxygen throughout the body.

placebo group; treatment group

Folic Acid DIETARY_SUPPLEMENT

Folic acid is a type of B vitamin that is normally found in foods such as dried beans, peas, lentils, oranges, whole-wheat products, liver, asparagus, beets, broccoli, brussels sprouts, and spinach. Folic acid helps your body produce and maintain new cells, and also helps prevent changes to DNA that may lead to cancer.

placebo group; treatment group

Eligibility Criteria

• Age: 25 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with unexplained RPL.
• Patients with abnormal immunological profile, including ANA, RF, anti-DNA, antilymphocyte, anticardiolipin, antithyroid and lupus anticoagulant antibodies that have no other clinical manifestation.
• Women with three or more pregnancy losses (before 24 weeks of gestation) who referred to the RPL clinic in Soroka hospital.
• An age above 25 years.
• The women agreed to participate in the study and signed on a consent form.
• women with index pregnancy.

You may not qualify if:

• Presence of any genetic impairment, Mullerian anomaly, endocrine or metabolic disorders, or a luteal-phase defect (as determined by a timed endometrial biopsy).
• Diabetes mellitus diagnosed by symptoms of diabetes plus random glucose concentration≥ 200mg/dL or fasting plasma glucose≥ 126mg/dL or hemoglobin A1C≥5.8% or 2-h plasma glucose≥ 200mg/dL during an oral glucose tolerance test.
• Previously untreated tuberculosis, as determined by an abnormal chest film in the previous year or a positive tuberculin skin test.
• Prednisone therapy during pregnancy for other reasons.
• Sensitivity to prednisone.

Sponsors & Collaborators

• Soroka University Medical Center: lead

Study Sites (1)

Soroka Medical Center

Beersheba, Israel

Location

Related Publications (24)

• ESHRE Guideline Group on RPL; Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Nelen W, Peramo B, Quenby S, Vermeulen N, Goddijn M. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open. 2018 Apr 6;2018(2):hoy004. doi: 10.1093/hropen/hoy004. eCollection 2018.

  PMID: 31486805 BACKGROUND

• (2) Mehta S, Gupta B. Recurrent Pregnancy Loss. 2018 Apr 20,.

  BACKGROUND

• Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009 Spring;2(2):76-83.

  PMID: 19609401 BACKGROUND

• Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012 Nov;98(5):1103-11. doi: 10.1016/j.fertnstert.2012.06.048. Epub 2012 Jul 24.

  PMID: 22835448 BACKGROUND

• Gabbai D, Harlev A, Friger M, Steiner N, Sergienko R, Kreinin A, Bashiri A. Pregnancy outcomes among patients with recurrent pregnancy loss and uterine anatomic abnormalities. J Perinat Med. 2018 Sep 25;46(7):728-734. doi: 10.1515/jpm-2016-0411. No abstract available.

  PMID: 28742523 BACKGROUND

• Kabessa M, Harlev A, Friger M, Sergienko R, Litwak B, Koifman A, Steiner N, Bashiri A. Pregnancy outcomes among patients with recurrent pregnancy loss and chromosomal aberration (CA) without PGD. J Perinat Med. 2018 Sep 25;46(7):764-770. doi: 10.1515/jpm-2016-0408. No abstract available.

  PMID: 28672755 BACKGROUND

• El Hachem H, Crepaux V, May-Panloup P, Descamps P, Legendre G, Bouet PE. Recurrent pregnancy loss: current perspectives. Int J Womens Health. 2017 May 17;9:331-345. doi: 10.2147/IJWH.S100817. eCollection 2017.

  PMID: 28553146 BACKGROUND

• Bashiri A, Gete S, Mazor M, Gete M. [Recurrent pregnancy loss--evaluation and treatment]. Harefuah. 2011 Nov;150(11):852-6, 875. Hebrew.

  PMID: 22428207 BACKGROUND

• Barnes PJ. How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol. 2006 Jun;148(3):245-54. doi: 10.1038/sj.bjp.0706736.

  PMID: 16604091 BACKGROUND

• Feldman PA, Wolfson D, Barkin JS. Medical management of Crohn's disease. Clin Colon Rectal Surg. 2007 Nov;20(4):269-81. doi: 10.1055/s-2007-991026.

  PMID: 20011423 BACKGROUND

• Bandoli G, Palmsten K, Forbess Smith CJ, Chambers CD. A Review of Systemic Corticosteroid Use in Pregnancy and the Risk of Select Pregnancy and Birth Outcomes. Rheum Dis Clin North Am. 2017 Aug;43(3):489-502. doi: 10.1016/j.rdc.2017.04.013.

  PMID: 28711148 BACKGROUND

• Hasegawa I, Takakuwa K, Goto S, Yamada K, Sekizuka N, Kanazawa K, Tanaka K. Effectiveness of prednisolone/aspirin therapy for recurrent aborters with antiphospholipid antibody. Hum Reprod. 1992 Feb;7(2):203-7. doi: 10.1093/oxfordjournals.humrep.a137617.

  PMID: 1577931 BACKGROUND

• Reznikoff-Etievant MF, Cayol V, Zou GM, Abuaf N, Robert A, Johanet C, Milliez J. Habitual abortions in 678 healthy patients: investigation and prevention. Hum Reprod. 1999 Aug;14(8):2106-9. doi: 10.1093/humrep/14.8.2106.

  PMID: 10438434 BACKGROUND

• Bansal AS, Bajardeen B, Thum MY. The basis and value of currently used immunomodulatory therapies in recurrent miscarriage. J Reprod Immunol. 2012 Jan;93(1):41-51. doi: 10.1016/j.jri.2011.10.002. Epub 2011 Dec 21.

  PMID: 22196105 BACKGROUND

• Ogasawara M, Aoki K. Successful uterine steroid therapy in a case with a history of ten miscarriages. Am J Reprod Immunol. 2000 Oct;44(4):253-5. doi: 10.1111/j.8755-8920.2000.440411.x.

  PMID: 11076099 BACKGROUND

• Gomaa MF, Elkholy AG, El-Said MM, Abdel-Salam NE. Combined oral prednisolone and heparin versus heparin: the effect on peripheral NK cells and clinical outcome in patients with unexplained recurrent miscarriage. A double-blind placebo randomized controlled trial. Arch Gynecol Obstet. 2014 Oct;290(4):757-62. doi: 10.1007/s00404-014-3262-0. Epub 2014 May 13.

  PMID: 24818590 BACKGROUND

• Quenby S, Kalumbi C, Bates M, Farquharson R, Vince G. Prednisolone reduces preconceptual endometrial natural killer cells in women with recurrent miscarriage. Fertil Steril. 2005 Oct;84(4):980-4. doi: 10.1016/j.fertnstert.2005.05.012.

  PMID: 16213853 BACKGROUND

• Quenby S, Farquharson R, Young M, Vince G. Successful pregnancy outcome following 19 consecutive miscarriages: case report. Hum Reprod. 2003 Dec;18(12):2562-4. doi: 10.1093/humrep/deg502.

  PMID: 14645171 BACKGROUND

• Tang AW, Alfirevic Z, Turner MA, Drury JA, Small R, Quenby S. A feasibility trial of screening women with idiopathic recurrent miscarriage for high uterine natural killer cell density and randomizing to prednisolone or placebo when pregnant. Hum Reprod. 2013 Jul;28(7):1743-52. doi: 10.1093/humrep/det117. Epub 2013 Apr 12.

  PMID: 23585559 BACKGROUND

• Tempfer CB, Kurz C, Bentz EK, Unfried G, Walch K, Czizek U, Huber JC. A combination treatment of prednisone, aspirin, folate, and progesterone in women with idiopathic recurrent miscarriage: a matched-pair study. Fertil Steril. 2006 Jul;86(1):145-8. doi: 10.1016/j.fertnstert.2005.12.035. Epub 2006 May 23.

  PMID: 16716321 BACKGROUND

• Kumar A. Immunomodulation in recurrent miscarriage. J Obstet Gynaecol India. 2014 Jun;64(3):165-8. doi: 10.1007/s13224-014-0541-4. Epub 2014 May 8.

  PMID: 24966498 BACKGROUND

• Wang SW, Zhong SY, Lou LJ, Hu ZF, Sun HY, Zhu HY. The effect of intravenous immunoglobulin passive immunotherapy on unexplained recurrent spontaneous abortion: a meta-analysis. Reprod Biomed Online. 2016 Dec;33(6):720-736. doi: 10.1016/j.rbmo.2016.08.025. Epub 2016 Sep 16.

  PMID: 27720163 BACKGROUND

• Laskin CA, Bombardier C, Hannah ME, Mandel FP, Ritchie JW, Farewell V, Farine D, Spitzer K, Fielding L, Soloninka CA, Yeung M. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N Engl J Med. 1997 Jul 17;337(3):148-53. doi: 10.1056/NEJM199707173370302.

  PMID: 9219700 BACKGROUND

• Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev. 2005 Apr 18;2005(2):CD002859. doi: 10.1002/14651858.CD002859.pub2.

  PMID: 15846641 BACKGROUND

MeSH Terms

Conditions

Abortion, Habitual

Interventions

Prednisone; Progesterone; Iron-Dextran Complex; Folic Acid

Condition Hierarchy (Ancestors)

Abortion, Spontaneous; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Coordination Complexes; Organic Chemicals; Dextrans; Glucans; Polysaccharides; Carbohydrates; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Asher Bashiri, Prof.

CONTACT

0505905738; abashiri@bgu.ac.il

Dalia Jbaren, medical student

CONTACT

0526907047; daliajb@post.bgu.ac.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: two groups. a treatment group and a placebo group

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: September 22, 2020
• Study Start: December 1, 2020
• Primary Completion: July 1, 2021
• Study Completion: October 1, 2021
• Last Updated: September 22, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)