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) (LOTUS II)

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)

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).

Study Overview

• Status: Completed
• Conditions: Female Infertility
• Intervention / Treatment: Drug: Dydrogesterone 30 mg; Drug: intravaginal progesterone gel 90 mg

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 1034
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • East Melbourne, Australia, 3002
    • Melbourne IVF
  • Kogarah, Australia, 2217
    • IVF Australia - St George Private HospitalIVF Australia - St George Private Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Univerité Catholique de Louvain, Cliniques universitaires Saint-Luc
  • Gent, Belgium, 9000
    • UZ Gent
  • Gent, Belgium, 9000
    • Algemeen Ziekenhuis Jan Palfijn Gent
  • Jette, Belgium, 1090
    • Universitair Ziekenhuis Brussel
• China
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Changsha, China, 410008
    • Reproductive & Genetic Hospital of Citic -Xiangya
  • Chengdu, China, 610041
    • West China Second University Hospital
  • Guangzhou, China, 510120
    • Sun Yat-Sen Memorial Hsopiatl, Sun Yat-Sen University
  • Guangzhou, China, 510655
    • The Sixth Hospital of Sun Yat-Sen University
  • Hefei, China, 230022
    • The First Affiliate Hospital of AnHui Medical University
  • Nanjing, China, 210029
    • The First Affiliated Hospital of Nanjing Medical University
  • Wuhan, China, 430030
    • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
  • Zhengzhou, China, 450052
    • First Affiliated Hospital of Zhengzhou University
• Germany
  • Berlin, Germany, 14050
    • Fertility Center Berlin
  • Bielefeld, Germany, 33619
    • Bielefeld Fertility Center
  • Dortmund, Germany, 44135
    • Kinderwunschzentrum Dortmund
  • Lübeck, Germany, 23538
    • Universitäres Kinderwunschzentrum Lübeck
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• India
  • Aurangabad, India, 431005
    • United CIIGMA Hospital
  • Bangalore, India, 560001
    • MILANN (Bangalore Assisted Conception Center)
  • Bangalore, India, 560076
    • Apollo Hospitals - Bangalore
  • Delhi, India, 110029
    • All India Institute of Medical Sciences
  • Delhi, India, 110057
    • Max Hospital
  • Kolkata, India, 700014
    • Institute of Reproductive Medicine
  • Lucknow, India, 226005
    • Ajanta Research Center, Ajanta Hospital and IVF center
  • Pune, India, 411002
    • Inamdar Multispecialty Hospital
  • Pune, India, 411006
    • Shree Hospital and Diagnostic Centre
• Russian Federation
  • Ekaterinburg, Russian Federation, 620043
    • CjSC "Center of Family Medicine"
  • Moscow, Russian Federation, 119192
    • CJSC "Nasledniki"
  • Moscow, Russian Federation, 117997
    • Scientific Research Center of Obstetrics, Gynecology and Perinatology n. a. Ac. V. I. Kulakova
  • Saint-Petersburg, Russian Federation, 193174
    • Saint-Petersburg State Budgetary Healtcare Institution "Maternity Hospital # 17"
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
• Thailand
  • Bangkok, Thailand, 90110
    • Songklanagarind Hospital
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
• Ukraine
  • Chernivtsi, Ukraine, 58022
    • Medical Centre of Infertility Treatment "Clinic of Professor Yuzko"
  • Kiev, Ukraine, 03037
    • "NADIYA" Clinic
  • Kiev, Ukraine, 04107
    • The Institute for Reproductive Medicine in Ukraine
  • Kiev, Ukraine, 0411
    • "Mother and Child" clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 39 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dydrogesterone tablets 3x10 mg	Drug: Dydrogesterone 30 mg; Oral Dydrogesterone 10 mg tablets tid
Experimental: Crinone 8% intravaginal progesterone gel 90 mg	Drug: intravaginal progesterone gel 90 mg; Other Names: Crinone 8% intravaginal progesterone gel 90 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound	Pregnancy rate defined as the presence of fetal heart beats at 12 weeks' gestation determined by transvaginal ultrasound.	12 weeks´ gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Pregnancy Test Rate (Percentage of Participants With a Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer)	Positive biochemical pregnancy test on Day 14 after embryo transfer	Day 14 after embryo transfer
Rate of Successful Completion of Pregnancy (Percentage of Participants With a Live Birth)	Live birth rate (percentage of participants with a live birth)	After delivery (about 9 months after IVF)
Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female)	The gender (number of delivered newborns that are male or female)	After delivery (about 9 months after IVF)

Collaborators and Investigators

• Sponsor: Abbott
• Collaborators: PRA Health Sciences; Datamap
• Investigators: Study Director: Shreyansh Shah, MD, Abbott

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: July 3, 2015
• First Posted (Estimate): July 8, 2015

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 4, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone; Dydrogesterone
• Other Study ID Numbers: M13-625; 2012-002993-29 (EudraCT Number)