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)

NCT ID: NCT02491437

Last Updated: 2019-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1034 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2017-05-31

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."

Conditions

Female Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dydrogesterone tablets 3x10 mg

Dydrogesterone tablets 3x10 mg

Group Type: EXPERIMENTAL

Dydrogesterone 30 mg

Intervention Type: DRUG

Oral Dydrogesterone 10 mg tablets tid

Crinone 8% intravaginal progesterone gel 90 mg

Crinone 8% intravaginal progesterone gel 90 mg

Group Type: EXPERIMENTAL

intravaginal progesterone gel 90 mg

Intervention Type: DRUG

Interventions

Dydrogesterone 30 mg

Oral Dydrogesterone 10 mg tablets tid

Intervention Type: DRUG

intravaginal progesterone gel 90 mg

Intervention Type: DRUG

Other Intervention Names

Crinone 8% intravaginal progesterone gel 90 mg

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 41 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

Datamap

INDUSTRY

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shreyansh Shah, MD

Role: STUDY_DIRECTOR

Abbott

Locations

Melbourne IVF

East Melbourne, , Australia

IVF Australia - St George Private HospitalIVF Australia - St George Private Hospital

Kogarah, , Australia

Univerité Catholique de Louvain, Cliniques universitaires Saint-Luc

Brussels, , Belgium

Algemeen Ziekenhuis Jan Palfijn Gent

Ghent, , Belgium

UZ Gent

Ghent, , Belgium

Universitair Ziekenhuis Brussel

Jette, , Belgium

Peking University People's Hospital

Beijing, , China

Reproductive & Genetic Hospital of Citic -Xiangya

Changsha, , China

West China Second University Hospital

Chengdu, , China

Sun Yat-Sen Memorial Hsopiatl, Sun Yat-Sen University

Guangzhou, , China

The Sixth Hospital of Sun Yat-Sen University

Guangzhou, , China

The First Affiliate Hospital of Anhui Medical University

Hefei, , China

The First Affiliated Hospital of Nanjing Medical University

Nanjing, , China

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, , China

First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Fertility Center Berlin

Berlin, , Germany

Bielefeld Fertility Center

Bielefeld, , Germany

Kinderwunschzentrum Dortmund

Dortmund, , Germany

Universitäres Kinderwunschzentrum Lübeck

Lübeck, , Germany

Queen Mary Hospital

Hong Kong, , Hong Kong

United CIIGMA Hospital

Aurangabad, , India

MILANN (Bangalore Assisted Conception Center)

Bangalore, , India

Apollo Hospitals - Bangalore

Bangalore, , India

All India Institute of Medical Sciences

Delhi, , India

Max Hospital

Delhi, , India

Institute of Reproductive Medicine

Kolkata, , India

Ajanta Research Center, Ajanta Hospital and IVF center

Lucknow, , India

Inamdar Multispecialty Hospital

Pune, , India

Shree Hospital and Diagnostic Centre

Pune, , India

Scientific Research Center of Obstetrics, Gynecology and Perinatology n. a. Ac. V. I. Kulakova

Moscow, , Russia

CJSC "Nasledniki"

Moscow, , Russia

Saint-Petersburg State Budgetary Healtcare Institution "Maternity Hospital # 17"

Saint Petersburg, , Russia

CJSC "Center of Family Medicine"

Yekaterinburg, , Russia

Singapore General Hospital

Singapore, , Singapore

Songklanagarind Hospital

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Medical Centre of Infertility Treatment "Clinic of Professor Yuzko"

Chernivtsi, , Ukraine

"NADIYA" Clinic

Kiev, , Ukraine

The Institute for Reproductive Medicine in Ukraine

Kiev, , Ukraine

"Mother and Child" clinic

Kiev, , Ukraine

Countries

Australia; Belgium; China; Germany; Hong Kong; India; Russia; Singapore; Thailand; Ukraine

References

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.

Reference Type: DERIVED

PMID: 30304457 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-002993-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M13-625

Identifier Type: -

Identifier Source: org_study_id