Clinical trial NCT01850030: A Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Intravaginal Micronized Progesterone Capsules 600 mg Daily for Luteal Support in In-Vitro Fertilization
Official title: A Double-Blind, Double-Dummy, Randomized, Two-arm, Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Intravaginal Micronized Progesterone Capsules 600 mg Daily for Luteal Support in In-Vitro Fertilization (Lotus I)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Female Infertility
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2013-05-09
Enrollment: 1070
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Female inability to conceive a child. The purpose of this randomized, two-arm and double blind, double dummy study is to demonstrate that the treatment of a daily dose of 3x10mg dydrogesterone orally is as effective and safe as the daily dose of 3x200 mg micronized progesterone capsules administered intravaginally for the luteal support in patients undergoing IVF. The treatment will start on the day of oocyte retrieval and continue until pregnancy is negative or until week 12 gestation.Patients will be followed after treatment until 30 days after delivery to record any safety and tolerability data of the patient and their newborn(s).


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Premenopausal females, age \> 18 years \< 42 years
* Non-smokers. For females who were past smokers, they must have stopped tobacco usage for at least 3 months prior baseline visit
* Early follicular phase (Day 2-4) Follicle stimulating hormone (FSH) less than or equal to 15 IU/L and estradiol (E2)within normal limits
* Luteinizing hormone (LH), prolactin (PRL), T (testosterone) and thyroid-stimulating hormone (TSH), within the normal limits for the clinical laboratory, or considered not clinically significant by the Investigator within 6 months prior to screening
* Documented history of infertility (e.g., unable to conceive for at least one year or for 6 months for women ≥ 38 years of age or bilateral tubal occlusion or absence)
* Normal transvaginal ultrasound at screening (or within 14 days of screening) without evidence of clinically significant abnormality consistent with finding adequate for Assisted Reproductive Technology (ART) with respect to uterus and adnexa (no hydrosalpinx or clinically relevant uterine fibroids)
* Negative pregnancy test on the day of pituitary down regulation (prior to administration of gonadotropin releasing hormones (GnRH) agonist or GnRH antagonist)
* Clinically indicated protocol for induction of IVF with a fresh embryo
* Single or dual embryo transfer
* BMI ≥ 18 and ≤ 30 kg/m2

Exclusion Criteria:

* Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic, hematologic/immunologic, head, ears, eyes, nose, throat (HEENT), dermatologic/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurologic/psychiatric, allergy, recent major surgery (\< 3 months), or other relevant diseases as revealed by history, physical examination and/or laboratory assessments which could limit participation in or completion of the study
* Acute urogenital disease
* Known allergic reactions to progesterone products
* Known allergic reactions to peanuts and peanut oil
* Intake of experimental drug or participation in any other clinical trial within 30 days prior to study start
* Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subjects to participate in or to complete the study
* Current or recent substance abuse, including alcohol and tobacco (Note: Patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed)
* History of chemotherapy or radiotherapy
* Patients with more than 3 unsuccessful IVF attempts
* Contraindication for pregnancy
* Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests
* History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages

Primary outcomes:
measure: Percentage of Participants Being Pregnant as Measured by the Presence of Fetal Heart Beats at 12 Weeks´Gestation Using Transvaginal Ultrasound
timeFrame: 12 weeks´ gestation (at visit 6)
Secondary outcomes:
measure: Percentage of Participants Being Pregnant as Measured by the Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer
timeFrame: Day 14 after embryo transfer
measure: Percentage of Participants With a Successful Completion of Pregnancy
timeFrame: After delivery (about 9 months after IVF)
measure: Gender of the Newborn
timeFrame: After delivery (about 9 months after IVF)
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Site reference no. 113176
city: Brasschaat
country: Belgium
facility: Site reference no. 93593
city: Brussels
country: Belgium
facility: Site reference no. 93598
city: Brussels
country: Belgium
facility: Site reference no. 93615
city: Brussels
country: Belgium
facility: Site reference no. 93617
city: Genk
country: Belgium
facility: Site reference no. 93613
city: Gent
country: Belgium
facility: Site reference no. 93594
city: Gent
country: Belgium
facility: Site reference no. 93597
city: Hasselt
country: Belgium
facility: Site reference no. 93616
city: Leuven
country: Belgium
facility: Site reference no. 93595
city: Mons
country: Belgium
facility: Site reference no. 93614
city: Helsinki
country: Finland
facility: Site reference ID ORG-000884
city: Jyväskylä
country: Finland
facility: Site reference ID ORG-000885
city: Oulu
country: Finland
facility: Site reference no. ORG-000635
city: Tampere
country: Finland
facility: Site reference ID ORG-000795
city: Turku
country: Finland
facility: Site reference no. ORG-000633
city: Berlin
country: Germany
facility: Site reference ID ORG-000645
city: Berlin
country: Germany
facility: Site reference ID ORG-000643
city: Dresden
country: Germany
facility: Site reference ID ORG-000642
city: Heidelberg
country: Germany
facility: Site reference ID ORG-000644
city: Luebeck
country: Germany
facility: Site reference ID ORG-000883
city: Be'er Sheva
country: Israel
facility: Site reference no. 93635
city: Hadera
country: Israel
facility: Research facility ID ORG-000934
city: Haifa
country: Israel
facility: Research facility ID ORG-000935
city: Jerusalem
country: Israel
facility: Site reference no. 93638
city: Tel Aviv
country: Israel
facility: Site reference no. 93641
city: Ekaterinburg
country: Russian Federation
facility: FSBI "Ural SRI of Maternity and Child Protection" of MoH and SD
city: Ekaterinburg
country: Russian Federation
facility: Center of Family Medicine LC
city: Moscow
country: Russian Federation
facility: FGBU Endocrinology Research Center of Minzdrav of Russia
city: Moscow
country: Russian Federation
facility: Moscow State Medical Dentistry University
city: Moscow
country: Russian Federation
facility: CJSC "Nasledniki"
city: Moscow
country: Russian Federation
facility: Moscow State Medical Dentistry University
city: St. Petersburg
country: Russian Federation
facility: SBEIHPE - NWSMU n.a.l.l.Melnichko MoH and SD of RF
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg SBHI "Maternity Hospital No 17" (main address)
city: Baracaldo, Vizcaya
country: Spain
facility: Site reference no. 119915
city: Barcelona
country: Spain
facility: Site reference ID ORG-000791
city: Bilbao
country: Spain
facility: Site reference no. ORG-000639
city: Pozuelo de Alarcon (Madrid)
country: Spain
facility: Site reference no. ORG-000640
city: Sevilla
country: Spain
facility: Site reference no. ORG-000638
city: Valencia
country: Spain
facility: Site reference no. ORG-000637
Study officials:
affiliation: Abbott
name: Darline Cheatham-Seitz, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Tournaye H, Sukhikh GT, Kahler E, Griesinger G. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod. 2017 May 1;32(5):1019-1027. doi: 10.1093/humrep/dex023.