Female InfertilityPhase 3LOTUS IINCT02491437
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)
A Phase 3 study testing Dydrogesterone 30 mg and intravaginal progesterone gel 90 mg in people with Female Infertility, run by Abbott at 40 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 to 41 years, women only
- Conditions the study is for
- Female Infertility
- What is being tested?
- Dydrogesterone 30 mg and intravaginal progesterone gel 90 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,034 participants
- Where
- 40 sitesin 10 countries
- Study dates
- Jul 2015to May 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 41 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
40 sites in 10 countries.
40 sites in 10 countries
China9 sites
Peking University People's Hospital
Beijing, 100044
Reproductive & Genetic Hospital of Citic -Xiangya
Changsha, 410008
West China Second University Hospital
Chengdu, 610041
Sun Yat-Sen Memorial Hsopiatl, Sun Yat-Sen University
Guangzhou, 510120
The Sixth Hospital of Sun Yat-Sen University
Guangzhou, 510655
The First Affiliate Hospital of Anhui Medical University
Hefei, 230022
The First Affiliated Hospital of Nanjing Medical University
Nanjing, 210029
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
Wuhan, 430030
First Affiliated Hospital of Zhengzhou University
Zhengzhou, 450052
India9 sites
MILANN (Bangalore Assisted Conception Center)
Bangalore, 560001
Apollo Hospitals - Bangalore
Bangalore, 560076
United CIIGMA Hospital
Chhatrapati Sambhajinagar, 431005
All India Institute of Medical Sciences
Delhi, 110029
Max Hospital
Delhi, 110057
Institute of Reproductive Medicine
Kolkata, 700014
Ajanta Research Center, Ajanta Hospital and IVF center
Lucknow, 226005
Inamdar Multispecialty Hospital
Pune, 411002
Shree Hospital and Diagnostic Centre
Pune, 411006
Belgium4 sites
Univerité Catholique de Louvain, Cliniques universitaires Saint-Luc
Brussels, 1200
Algemeen Ziekenhuis Jan Palfijn Gent
Ghent, 9000
UZ Gent
Ghent, 9000
Universitair Ziekenhuis Brussel
Jette, 1090
Germany4 sites
Fertility Center Berlin
Berlin, 14050
Bielefeld Fertility Center
Bielefeld, 33619
Kinderwunschzentrum Dortmund
Dortmund, 44135
Universitäres Kinderwunschzentrum Lübeck
Lübeck, 23538
Russia4 sites
Scientific Research Center of Obstetrics, Gynecology and Perinatology n. a. Ac. V. I. Kulakova
Moscow, 117997
CJSC "Nasledniki"
Moscow, 119192
Saint-Petersburg State Budgetary Healtcare Institution "Maternity Hospital # 17"
Saint Petersburg, 193174
CJSC "Center of Family Medicine"
Yekaterinburg, 620043
Ukraine4 sites
Medical Centre of Infertility Treatment "Clinic of Professor Yuzko"
Chernivtsi, 58022
"NADIYA" Clinic
Kiev, 03037
The Institute for Reproductive Medicine in Ukraine
Kiev, 04107
"Mother and Child" clinic
Kiev, 0411
Australia2 sites
Melbourne IVF
East Melbourne, 3002
IVF Australia - St George Private HospitalIVF Australia - St George Private Hospital
Kogarah, 2217
Thailand2 sites
Songklanagarind Hospital
Bangkok, 90110
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200
About this study
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)
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).
Read the detailed description
"This article has been accepted for publication in Human Reproduction published by Oxford University Press."
- Conditions
- Female Infertility
- Being tested
- Dydrogesterone 30 mg, intravaginal progesterone gel 90 mg
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dydrogesterone 30 mgDrug
Oral Dydrogesterone 10 mg tablets tid
intravaginal progesterone gel 90 mgDrug
Also called Crinone 8% intravaginal progesterone gel 90 mg
| Study group | Role | What they receive |
|---|---|---|
| Dydrogesterone tablets 3x10 mg | Experimental | Dydrogesterone tablets 3x10 mg Receives: Drug: Dydrogesterone 30 mg |
| Crinone 8% intravaginal progesterone gel 90 mg | Experimental | Crinone 8% intravaginal progesterone gel 90 mg Receives: Drug: intravaginal progesterone gel 90 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks´ gestation
Secondary outcomes (3)
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
Measured: 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)
Measured: 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)
Measured: After delivery (about 9 months after IVF)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2015 (estimated)
- Study startJul 2015
- Primary completionMay 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Female InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,034 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abbott
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences, Datamap
- Responsible party
- Sponsor
- Investigators
- Shreyansh Shah, MD, Study director, Abbott
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02491437
- Sponsor's protocol ID
- M13-625
- Other IDs
- 2012-002993-29
- Acronym
- LOTUS II
- Status last verified
- Sep 2019
- First submitted
- 16 Jun 2015
- Last updated
- 1 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 30304457
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02491437
- Acronym / sponsor ID
- LOTUS II / M13-625
- Conditions
- Female Infertility
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,034 participants (actual)
- Lead sponsor
- AbbottIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences, Datamap
- Study start
- Jul 2015
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 8 Jul 2015 (estimated)
- Results
- Posted 1 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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."
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dydrogesterone tablets 3x10 mg | Experimental | Drug: Dydrogesterone 30 mgDydrogesterone tablets 3x10 mg |
| Crinone 8% intravaginal progesterone gel 90 mg | Experimental | Drug: intravaginal progesterone gel 90 mgCrinone 8% intravaginal progesterone gel 90 mg |
Who may qualify
- Ages
- 19 to 41 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dydrogesterone 30 mgOral Dydrogesterone 10 mg tablets tid | Drug | Dydrogesterone tablets 3x10 mg |
| intravaginal progesterone gel 90 mgAlso: Crinone 8% intravaginal progesterone gel 90 mg | Drug | Crinone 8% intravaginal progesterone gel 90 mg |
Primary outcome
Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound
Time frame: 12 weeks´ gestation
Pregnancy rate defined as the presence of fetal heart beats at 12 weeks' gestation determined by transvaginal ultrasound.
3 secondary outcomes
Positive Pregnancy Test Rate (Percentage of Participants With a Positive Biochemical Pregnancy Test on Day 14 After Embryo Transfer)
Time frame: Day 14 after embryo transfer
Rate of Successful Completion of Pregnancy (Percentage of Participants With a Live Birth)
Time frame: After delivery (about 9 months after IVF)
Physical Examination Newborn (Number of Delivered Newborns That Are Male or Female)
Time frame: After delivery (about 9 months after IVF)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30304457Griesinger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shreyansh Shah, MD study director
Abbott
40 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dydrogesterone 30 mg and intravaginal progesterone gel 90 mg in people with Female Infertility, run by Abbott at 40 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in China, India, Belgium, Germany, Russia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Presence of Fetal Heart Beats at 12 Week's Gestation Determined by Transvaginal Ultrasound (time frame: 12 weeks´ gestation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02491437, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2019.