Ignite Creation Date:
2025-12-24 @ 3:02 PM
Ignite Modification Date:
2025-12-29 @ 5:40 AM
Study NCT ID:
NCT03440359
Status:
COMPLETED
Last Update Posted:
2018-02-26
First Post:
2018-02-07
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Vaginal Progesterone Supplementation in Women With PCOS Undergoing Ovulation Induction With Letrozole
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011085', 'term': 'Polycystic Ovary Syndrome'}], 'ancestors': [{'id': 'D010048', 'term': 'Ovarian Cysts'}, {'id': 'D003560', 'term': 'Cysts'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D010049', 'term': 'Ovarian Diseases'}, {'id': 'D000291', 'term': 'Adnexal Diseases'}, {'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D006058', 'term': 'Gonadal Disorders'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C400424', 'term': 'Crinone'}, {'id': 'D014622', 'term': 'Vaginal Creams, Foams, and Jellies'}, {'id': 'D000077289', 'term': 'Letrozole'}, {'id': 'C412828', 'term': 'Ovidrel'}], 'ancestors': [{'id': 'D004304', 'term': 'Dosage Forms'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D053566', 'term': 'Feminine Hygiene Products'}, {'id': 'D004864', 'term': 'Equipment and Supplies'}, {'id': 'D009570', 'term': 'Nitriles'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR'], 'maskingDescription': 'Data analysis was completed by blinded observer who had access only to participant ID number, cycle number and treatment, and pregnancy outcome'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants who met criteria were randomized to either Crinone vaginal therapy versus no therapy in the luteal phase of an ovulation induction cycle. Participants who did not achieve a pregnancy were able to participate in up to 3 cycles, and were re-randomized with each cycle.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 52}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-07-06', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-02', 'completionDateStruct': {'date': '2017-12-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-02-23', 'studyFirstSubmitDate': '2018-02-07', 'studyFirstSubmitQcDate': '2018-02-14', 'lastUpdatePostDateStruct': {'date': '2018-02-26', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-02-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-11-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Clinical pregnancy rates', 'timeFrame': 'Per initiated cycle of treatment. At the end of Cycle 1, 2, and 3 (each cycle is 28 days) and if pregnant up to 8 weeks after completion of cycle', 'description': 'The primary endpoint of the trial is the Clinical Pregnancy Rate per cycle initiated'}], 'secondaryOutcomes': [{'measure': 'Live birth rates', 'timeFrame': 'Up to 1 year or until delivery', 'description': 'The secondary endpoint is the Live Birth Rate per cycle initiated (each cycle is 28 days)'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['PCOS, crinone, vaginal progesterone, ovulation induction'], 'conditions': ['Polycystic Ovary Syndrome']}, 'referencesModule': {'references': [{'pmid': '14560891', 'type': 'BACKGROUND', 'citation': 'Franks S. Assessment and management of anovulatory infertility in polycystic ovary syndrome. Endocrinol Metab Clin North Am. 2003 Sep;32(3):639-51. doi: 10.1016/s0889-8529(03)00044-6.'}, {'pmid': '13899931', 'type': 'BACKGROUND', 'citation': 'GOLDZIEHER JW, GREEN JA. The polycystic ovary. I. Clinical and histologic features. J Clin Endocrinol Metab. 1962 Mar;22:325-38. doi: 10.1210/jcem-22-3-325. No abstract available.'}, {'pmid': '12952386', 'type': 'BACKGROUND', 'citation': 'Richardson MR. Current perspectives in polycystic ovary syndrome. Am Fam Physician. 2003 Aug 15;68(4):697-704.'}, {'pmid': '12958117', 'type': 'BACKGROUND', 'citation': 'Hamilton-Fairley D, Taylor A. Anovulation. BMJ. 2003 Sep 6;327(7414):546-9. doi: 10.1136/bmj.327.7414.546. No abstract available.'}, {'pmid': '9637695', 'type': 'BACKGROUND', 'citation': 'Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest. 1998 Jun 15;101(12):2622-9. doi: 10.1172/JCI2081.'}, {'pmid': '14711538', 'type': 'BACKGROUND', 'citation': 'Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004.'}, {'pmid': '19127427', 'type': 'BACKGROUND', 'citation': 'Ganesh A, Goswami SK, Chattopadhyay R, Chaudhury K, Chakravarty B. Comparison of letrozole with continuous gonadotropins and clomiphene-gonadotropin combination for ovulation induction in 1387 PCOS women after clomiphene citrate failure: a randomized prospective clinical trial. J Assist Reprod Genet. 2009 Jan;26(1):19-24. doi: 10.1007/s10815-008-9284-4. Epub 2009 Jan 7.'}, {'pmid': '17604615', 'type': 'BACKGROUND', 'citation': 'Casper RF. Aromatase inhibitors in ovarian stimulation. J Steroid Biochem Mol Biol. 2007 Aug-Sep;106(1-5):71-5. doi: 10.1016/j.jsbmb.2007.05.025. Epub 2007 May 24.'}, {'pmid': '19584394', 'type': 'BACKGROUND', 'citation': 'Eckmann KR, Kockler DR. Aromatase inhibitors for ovulation and pregnancy in polycystic ovary syndrome. Ann Pharmacother. 2009 Jul;43(7):1338-46. doi: 10.1345/aph.1M096. Epub 2009 Jul 7.'}, {'pmid': '8062942', 'type': 'BACKGROUND', 'citation': 'Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril. 1994 Sep;62(3):485-90. doi: 10.1016/s0015-0282(16)56935-0.'}, {'pmid': '15652895', 'type': 'BACKGROUND', 'citation': 'Cortinez A, De Carvalho I, Vantman D, Gabler F, Iniguez G, Vega M. Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients. Fertil Steril. 2005 Jan;83(1):110-5. doi: 10.1016/j.fertnstert.2004.05.099.'}, {'pmid': '19515366', 'type': 'BACKGROUND', 'citation': 'Montville CP, Khabbaz M, Aubuchon M, Williams DB, Thomas MA. Luteal support with intravaginal progesterone increases clinical pregnancy rates in women with polycystic ovary syndrome using letrozole for ovulation induction. Fertil Steril. 2010 Jul;94(2):678-83. doi: 10.1016/j.fertnstert.2009.03.088. Epub 2009 Jun 9.'}]}, 'descriptionModule': {'briefSummary': 'Aromatase inhibitors such as letrozole are hypothesized to maintain normal hypothalamic/ pituitary feedback mechanisms and in the case of OI (ovulation induction) in women with PCOS, may act to increase follicular sensitivity to FSH by increasing intrafollicular androgen levels. Letrozole also may act to increase midluteal P levels presumably by induction of follicles and corpora lutea. The investigators are asking the question whether P supplementation with Crinone (8%) may have an additive beneficial effect on endometrial development in those women taking letrozole. Progesterone levels in the endometrium (tissue levels) have been documented to be significantly higher than serum levels after vaginal administration which may lead to higher pregnancy rates. In addition P has been shown to decrease LH pulse frequency which is elevated in PCOS and has been shown to down regulate endometrial androgen receptors. There have been retrospective studies showing progesterone supplementation seems to benefit both CC and letrozole treatment groups. In fact, this study showed the only pregnancies in the letrozole group were those in women who took P supplementation. However the number of cycles studied was small. There is a place for a randomized controlled trial (RCT) to determine if luteal phase P supplementation with Crinone should be used in all women using letrozole for Ovulation Induction (OI) in combination with Intrauterine Insemination (IUI) or Timed Intercourse (TI). This is currently not done in all clinical practices.', 'detailedDescription': "Approval of the study was obtained from the local IRB. Prospective volunteers had had an infertility workup including blood hormone levels (FSH, LH, E2, Progesterone, Prolactin, and Thyroid), partner's semen analysis, HSG, laparoscopy or hydrosonogram, plus a baseline evaluation including ultrasound of ovaries and uterus performed as standard of care. If the results of these tests and the remaining Inclusion/Exclusion criteria were met, the study consent was reviewed with participants and signatures were obtained. Participants contacted the clinic at the start of their menses (spontaneous or progesterone-induced) to start the treatment cycle. Eligibility criteria was reviewed, and Letrozole 2.5-7.5 mg day 3-7 was initiated based on BMI and prior response. An ultrasound was performed on cycle day 11 or 12 and repeated if needed to determine response until at least 1 follicle with mean diameter \\> 17mm in size was observed. When the appropriate follicle size was reached, participants were randomized into one of the two treatment groups as determined by a randomization table, and Ovidrel (250mcg) was administered. If there was no response identified by follicle growth on day 21, the participant was considered a letrozole failure, the cycle was stopped, and the participant was dropped from the study and was not included in subsequent cycles.\n\nIUI/TI was performed at 24-48 hours after the Ovidrel (hCG) injection. If the participant was randomized to progesterone (Crinone), the luteal phase was supplemented once daily with vaginal progesterone (Crinone 8%) starting the second day after the IUI or TI and continued for 14 days. A urine or serum pregnancy test was performed as standard of care 16 days after the IUI/TI. If the test was positive, a confirmatory blood level (βhCG) was performed as standard of care X2 (1 week apart) and an ultrasound on post-hCG day 35-42 was done. Any pregnancies occurring in either treatment group were followed for delivery outcomes. Information regarding the delivery (induced, vaginal, cesarean section), date of birth, infant measurements (weight and length) and other important information regarding the infant's condition was obtained. Participants were allowed to undergo up to 3 cycles of letrozole as the pregnancy rates for the first 3 cycles have been shown to be similar. The participants were re-randomized each cycle. If the participant was pregnant, Crinone (8%) was continued until 10 weeks gestation in both groups.\n\nEach participant was able to proceed with up to 3 cycles (consecutively, if desired) of OI over the next 6 months and was re-randomized each cycle."}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '40 Years', 'minimumAge': '20 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Women who have anovulatory or oligoovulatory infertility who are undergoing ovulation induction for infertility with TI or IUI , with or without regular cycles defined as cycle length \\> 35 days, \\< 26 days or amenorrhea (no cycles in the past six months), and who meet 2 out of 3 of the Rotterdam Criteria (1. Chronic anovulation or irregular cycles, 2. Clinical or biochemical hyperandrogenism, 3. Polycystic appearing ovaries on ultrasound.)\n* Day 3 FSH(Follicle stimulating hormone)\\< 10 (obtained within 2 years prior to screening\n* Documented infertility for at least 1 year or documented anovulation\n* Willing to participate in up to 3 cycles of OI with letrozole and IUI or TI\n* Partner's or donor's SA\\> 5 million motile sperm within 2 years of screening\n* Patients may have received clomiphene citrate or letrozole treatment in the past.\n\nExclusion Criteria:\n\n* Untreated thyroid or prolactin abnormalities\n* Pregnancy in the last 3 months\n* BMI\\< 18 or \\>40kg/m2\n* Abnormal uterine bleeding of undetermined origin\n* Contraindications to pregnancy\n* Progesterone sensitivity\n* Uterine anomalies seen on ultrasound (performed within 6 months prior to screening) that can affect pregnancy chances such as submucosal uterine fibroids or polyps\n* Three or more previous consecutive pregnancy losses\n* Blocked fallopian tubes X2 (documented by HSG, laparoscopy, or hydrosonogram completed within past 3 years)\n* More than 3 failed monitored letrozole cycles prior to enrolling"}, 'identificationModule': {'nctId': 'NCT03440359', 'briefTitle': 'Vaginal Progesterone Supplementation in Women With PCOS Undergoing Ovulation Induction With Letrozole', 'organization': {'class': 'OTHER', 'fullName': 'Eastern Virginia Medical School'}, 'officialTitle': '"Supplementation of the Luteal Phase With Vaginal Progesterone (Crinone 8%) in Women With Polycystic Ovary Syndrome Undergoing Ovulation Induction With Letrozole: A Prospective and Randomized Controlled Trial', 'orgStudyIdInfo': {'id': 'IRB 12-07-FB-0170'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': '# 1- no progesterone therapy', 'description': 'Letrrozole 2.5 to 5 mg oral tablet cycle day 3-7.Pelvic ultrasound at cycle day 11 or 12 and repeat if needed until leading follicle is \\>17 mm. Ovidrel 250 mcg injected sq. Timed intercourse or intrauterine insemination. No supplemental progesterone therapy in luteal phase', 'interventionNames': ['Drug: Letrozole Oral Tablet', 'Diagnostic Test: pelvic ultrasound', 'Drug: Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe', 'Other: Intrauterine insemination or timed intercourse']}, {'type': 'ACTIVE_COMPARATOR', 'label': '# 2 - Progesterone Vaginal Gel 8%', 'description': 'Letrrozole 2.5 to 5 mg oral tablet cycle day 3-7. Pelvic ultrasound at cycle day 11 or 12 and repeat if needed until leading follicle is \\>17 mm. Ovidrel 250 mcg injected sq. Timed intercourse or intrauterine insemination.Crinone 8% (progesterone) vaginal therapy was provided in luteal phase for 14 days .Administration was started the second day after intrauterine insemination or timed intercourse.', 'interventionNames': ['Drug: Progesterone Vaginal Gel 8%', 'Drug: Letrozole Oral Tablet', 'Diagnostic Test: pelvic ultrasound', 'Drug: Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe', 'Other: Intrauterine insemination or timed intercourse']}], 'interventions': [{'name': 'Progesterone Vaginal Gel 8%', 'type': 'DRUG', 'otherNames': ['Crinone 8% vaginal gel'], 'description': 'progesterone supplementation for luteal phase support administered with vaginal applicators and used instead of progesterone intramuscular injections or progesterone vaginal suppositories.', 'armGroupLabels': ['# 2 - Progesterone Vaginal Gel 8%']}, {'name': 'Letrozole Oral Tablet', 'type': 'DRUG', 'description': 'letrozole oral tablet 2.5 mg or 5 mg administered cycle day 3-7 for ovulation induction', 'armGroupLabels': ['# 1- no progesterone therapy', '# 2 - Progesterone Vaginal Gel 8%']}, {'name': 'pelvic ultrasound', 'type': 'DIAGNOSTIC_TEST', 'description': 'pelvic ultrasound performed at cycle day 11 or 12 and repeated as necessary until leading follicle size is \\>17 mm in diameter', 'armGroupLabels': ['# 1- no progesterone therapy', '# 2 - Progesterone Vaginal Gel 8%']}, {'name': 'Ovidrel 250 MCG Per 0.5 ML Prefilled Syringe', 'type': 'DRUG', 'otherNames': ['recombinant hCG 250 mcg'], 'description': 'ovidrel 250 mcg given when leading follicle size is \\> 17 mm in diameter', 'armGroupLabels': ['# 1- no progesterone therapy', '# 2 - Progesterone Vaginal Gel 8%']}, {'name': 'Intrauterine insemination or timed intercourse', 'type': 'OTHER', 'description': 'Intrauterine insemination or timed intercourse (depending on semen parameters) performed 36-40 hours after Ovidrel', 'armGroupLabels': ['# 1- no progesterone therapy', '# 2 - Progesterone Vaginal Gel 8%']}]}, 'contactsLocationsModule': {'locations': [{'zip': '23507', 'city': 'Norfolk', 'state': 'Virginia', 'country': 'United States', 'facility': 'Laurel A. Stadtmauer, MD, PhD', 'geoPoint': {'lat': 36.84681, 'lon': -76.28522}}], 'overallOfficials': [{'name': 'Laurel A Stadtmauer, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Eastern Virginia Medical School'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Eastern Virginia Medical School', 'class': 'OTHER'}, 'collaborators': [{'name': 'Watson Pharmaceuticals', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Laurel Stadtmauer', 'investigatorAffiliation': 'Eastern Virginia Medical School'}}}}