Clinical trial NCT02491437: A Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Crinone 8% Intravaginal Progesterone Gel 90 mg Daily for Luteal Support in In-Vitro Fertilization (LOTUS II)
Official title: A Randomized, Open-label, Two-arm, Multicenter Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone 30 mg Daily Versus Crinone 8% Intravaginal Progesterone Gel 90 mg Daily for Luteal Support in In-Vitro Fertilization (LOTUS II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Female Infertility
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
name: Datamap
First posted: 2015-07-08
Enrollment: 1034
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: The purpose of this randomized, two-arm and open label study is to demonstrate that the treatment of a daily dose of 3x10mg dydrogesterone orally is as effective and safe as the daily dose Crinone 8% intravaginal progesterone gel 90 mg for the luteal support in women who are unable to conceive a child and are 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 during treatment until 30 days after delivery to record any safety and tolerability data of the patient and their newborn (s).

Detailed description: "This article has been accepted for publication in Human Reproduction published by Oxford University Press."

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 screening 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 at screening
* 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 or at 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 prior 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)
* Subject is not pregnant , confirmed by negative pregnancy or by Investigator Judgement
* 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, HEENT (head, ears, eyes, nose, throat), 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 àny experimental drug or any 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 Acute urogenital disease

Primary outcomes:
measure: Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound
timeFrame: 12 weeks´ gestation
Secondary outcomes:
measure: Positive Pregnancy Test Rate (Percentage of Participants With a Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer)
timeFrame: Day 14 after embryo transfer
measure: Rate of Successful Completion of Pregnancy (Percentage of Participants With a Live Birth)
timeFrame: After delivery (about 9 months after IVF)
measure: Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female)
timeFrame: After delivery (about 9 months after IVF)
Other outcomes:
Locations:
city: East Melbourne
country: Australia
facility: Melbourne IVF
city: Kogarah
country: Australia
facility: IVF Australia - St George Private HospitalIVF Australia - St George Private Hospital
city: Brussels
country: Belgium
facility: Univerité Catholique de Louvain, Cliniques universitaires Saint-Luc
city: Gent
country: Belgium
facility: Algemeen Ziekenhuis Jan Palfijn Gent
city: Gent
country: Belgium
facility: UZ Gent
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Beijing
country: China
facility: Peking University People's Hospital
city: Changsha
country: China
facility: Reproductive & Genetic Hospital of Citic -Xiangya
city: Chengdu
country: China
facility: West China Second University Hospital
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hsopiatl, Sun Yat-Sen University
city: Guangzhou
country: China
facility: The Sixth Hospital of Sun Yat-Sen University
city: Hefei
country: China
facility: The First Affiliate Hospital of Anhui Medical University
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
city: Berlin
country: Germany
facility: Fertility Center Berlin
city: Bielefeld
country: Germany
facility: Bielefeld Fertility Center
city: Dortmund
country: Germany
facility: Kinderwunschzentrum Dortmund
city: Lübeck
country: Germany
facility: Universitäres Kinderwunschzentrum Lübeck
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Aurangabad
country: India
facility: United CIIGMA Hospital
city: Bangalore
country: India
facility: MILANN (Bangalore Assisted Conception Center)
city: Bangalore
country: India
facility: Apollo Hospitals - Bangalore
city: Delhi
country: India
facility: All India Institute of Medical Sciences
city: Delhi
country: India
facility: Max Hospital
city: Kolkata
country: India
facility: Institute of Reproductive Medicine
city: Lucknow
country: India
facility: Ajanta Research Center, Ajanta Hospital and IVF center
city: Pune
country: India
facility: Inamdar Multispecialty Hospital
city: Pune
country: India
facility: Shree Hospital and Diagnostic Centre
city: Ekaterinburg
country: Russian Federation
facility: CJSC "Center of Family Medicine"
city: Moscow
country: Russian Federation
facility: Scientific Research Center of Obstetrics, Gynecology and Perinatology n. a. Ac. V. I. Kulakova
city: Moscow
country: Russian Federation
facility: CJSC "Nasledniki"
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Budgetary Healtcare Institution "Maternity Hospital # 17"
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Bangkok
country: Thailand
facility: Songklanagarind Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Chernivtsi
country: Ukraine
facility: Medical Centre of Infertility Treatment "Clinic of Professor Yuzko"
city: Kiev
country: Ukraine
facility: "NADIYA" Clinic
city: Kiev
country: Ukraine
facility: The Institute for Reproductive Medicine in Ukraine
city: Kiev
country: Ukraine
facility: "Mother and Child" clinic
Study officials:
affiliation: Abbott
name: Shreyansh Shah, MD
role: STUDY_DIRECTOR
References:
citation: Griesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, Chen ZJ, Kahler E, Pexman-Fieth C, Tournaye H. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod. 2018 Dec 1;33(12):2212-2221. doi: 10.1093/humrep/dey306.