| CTRI Number |
CTRI/2016/01/006490 [Registered on: 07/01/2016] Trial Registered Prospectively |
| Last Modified On: |
19/10/2016 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A Study Comparing the Efficacy, Safety and Tolerability of Oral Dydrogesterone versus Crinone intravaginal progesterone gel for Luteal Support in In-Vitro Fertilization (LOTUS II) |
|
Scientific Title of Study
|
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) |
| Trial Acronym |
Lotus II |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| M13-625 |
Protocol Number |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
DrSonia Malik |
| Designation |
Consultant |
| Affiliation |
Max Hospital |
| Address |
Max Hospital
B- Block, Sushant Lok – l, Gurgaon, Haryana, India
122001
Gurgaon
HARYANA
122001
India |
| Phone |
|
| Fax |
|
| Email |
sm_doc@hotmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
DrShubhangi Desai |
| Designation |
Head- Clinical Operations and Pharmacovigilance |
| Affiliation |
Abbott India Limited |
| Address |
Abbott India Limited
271, Business Park, 6th Flr
Model Industrial Colony
Off Aarey Road
Goregaon (E)
Mumbai 400 063
India
Mumbai
MAHARASHTRA
400 063
India |
| Phone |
|
| Fax |
|
| Email |
shubhangi.desai@abbott.com |
|
Details of Contact Person
Public Query
|
| Name |
DrBalagopal Nair |
| Designation |
Director Medical affairs - EPD |
| Affiliation |
Abbott India Limited |
| Address |
Abbott India Limited
271, Business Park, 6th Flr
Model Industrial Colony
Off Aarey Road
Goregaon (E)
Mumbai 400 063
India
Mumbai
MAHARASHTRA
400 063
India |
| Phone |
|
| Fax |
|
| Email |
balagopal.nair@abbott.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Abbott Laboratories GmbH |
| Address |
Freundallee 9A
D-30173 Hannover |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India
Australia
Belgium
China
Germany
Hong Kong
Russian Federation
Singapore
Thailand
Ukraine |
Sites of Study
Modification(s)
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Gita Khanna |
Ajanta Research |
Ajanta Research
Centre, Ajanta
Hospital and IVF
Centre.
765, ABC
Complex,
Alambagh,
Lucknow, Uttar
Pradesh, India.
PIN-226005
Lucknow
UTTAR PRADESH |
05224101017
ivfajanta@gmail.com |
| Dr Alka Kriplani |
All India Institute of Medical Sciences |
Department of
Obstetrics &
Gynecology,
Room No 3076,
3rd Block, All
India Institute of
Medical Sciences,
Ansari Nagar,
New Delhi, India
PIN-110029
New Delhi
DELHI |
01126593221
kriplanialka@gmail.com |
| Chitra Ramamurthy |
Apollo Hospital |
154/11, Opp. IIMB, Bannerghatta Road, Bangalore, Karnataka - 560076
Bangalore
KARNATAKA |
080236304017
bingiramamurty@yahoo.co.in |
| Dr Amit Mohan Shah |
Inamdar Multispeciality Hospital |
Hospital Building, S,No.15, Fatima Nagar, Pune - 411040
Pune
MAHARASHTRA |
02066812357
dramitshah@yahoo.com |
| DrSonia Malik |
Max Hospital |
Max Hospital
B- Block, Sushant Lok – l, Gurgaon, Haryana, India
122001
Gurgaon
HARYANA |
911246623000
sm_doc@hotmail.com |
| Dr Kamini Rao |
Milann Fertility Center, BACC Healthcare Pvt Ltd |
Milann Fertility Center, BACC Healthcare Pvt Ltd, No 7 & East Park Road, Kumara Parak East, Bangalore, Karnataka, India. Pin-560001
Bangalore
KARNATAKA |
08022343391
drkaminirao@gmail.com |
| Dr Bharati Dhorepatil |
Shree Hospital & Diagnostic Center |
Shree Hospital & Diagnostic Center, Pune Nagar Road, Opp. Agakhan Palace, near Shastri Nagar Bus stop, Pune Maharashtra 411006
Pune
MAHARASHTRA |
912026681127
gesipune@gmail.com |
| Dr Paayal Chobe |
United CIIGMA Institute of Medical Sciences Pvt Ltd |
Department of Genesis IVF and Endoscopy Centre LLP,
United CIIGMA Institute of Medical Sciences Pvt Ltd
Shahnoorwadi Dargah Road.
Aurangabad.
Maharashtra, India. PIN-431005
Aurangabad
MAHARASHTRA |
02402335751
drpayaluch@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Ethics Committee Kodlikeri Memorial Hospital and CIIGMA Hospital |
Approved |
| Ethics Committee, Ajanta Hospital and IVF Centre |
Approved |
| Ethics Committee, Inamdar Hospital |
Approved |
| IIRRH-BACC Healthcare Institutional Ethics Committee |
Approved |
| Institute Ethics Committee All india Institute of medical sciences |
Approved |
| Institutional Ethics Commitee, Apollo Hospitals |
Approved |
| Max Healthcare Ethics Committee |
Approved |
| The Ethics Committee of Shree Hospital |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Female infertility, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Crinone 8% intravaginal progesterone gel |
Dose: 90 mg
Frequency: Once daily
Duration: Until pregnancy is negative or until week 12 gestation
Route of administration: Intra-vaginal |
| Intervention |
Dydrogesterone tablets |
Dose: 10 mg
Frequency: Three times a day
Duration: Until pregnancy is negative or until week 12 gestation
Route of administration: Oral |
|
|
Inclusion Criteria
|
| Age From |
19.00 Year(s) |
| Age To |
41.00 Year(s) |
| Gender |
Female |
| Details |
1. Signed informed consent;
2. Premenopausal females, age > 18 years < 42 years
3. Non-smokers. For females who were past smokers, they must have
stopped tobacco usage for at least 3 months prior baseline visit
4. Early follicular phase (Day 2-4) FSH (Follicle stimulating hormone)
less than or equal to 15 IU/L and estradiol (E2)within normal limits
5. LH (luteinizing hormone), PRL (prolactin), T (testosterone) and TSH
(thyroid-stimulating hormone), within the normal limits for the clinical
laboratory, or considered not clinically significant by the Investigator
within 6 months prior to screening
6. 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)
7. Normal transvaginal ultrasound at screening (or within 14 days of
screening) without evidence of clinically significant abnormality
consistent with finding adequate for ART with respect to uterus and
adnexa (no hydrosalpinx or clinically relevant uterine fibroids)
8. Negative pregnancy test on the day of pituitary down regulation (prior
to administration of GnRH agonist or GnRH antagonist)
9. Clinically indicated protocol for induction of IVF with a fresh embryo
10. Single or dual embryo transfer
11. BMI ≥ 18 and ≤ 30 kg/m2 |
|
| ExclusionCriteria |
| Details |
1.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
2.Acute urogenital disease
3.Known allergic reactions to progesterone products
4.Intake of experimental drug or any participation in any other clinical trial within 30 days prior to study start
5.Mental disability or any other lack of fitness, in the investigators opinion, to preclude subjects in or to complete the study
6.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)
7.History of chemotherapy
8.Patients with more than 3 unsuccessful IVF attempts
9.Contraindication for pregnancy
10.Refusal or inability to comply with the requirements of the study protocol for any reason,
including scheduled clinic visits and laboratory tests
11.History of recurrent pregnancy loss defined as 3 or more spontaneous miscarriages |
|
|
Method of Generating Random Sequence
|
|
|
Method of Concealment
|
|
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Pregnancy rate defined as the presence of fetal heart beats at 12 weeks’ gestation determined by transvaginal ultrasound. |
Pregnancy rate defined as the presence of fetal heart beats at 12 weeks’ gestation determined by transvaginal ultrasound. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Positive biochemical pregnancy test on Day 14 after embryo transfer |
Day 14 after embryo transfer |
| Rate of successful completion of pregnancy (Incidence of live births and healthy newborns) |
After delivery (about 9 months after IVF) |
| Adverse Events (Safety and Tolerability data (mother and child) ) |
until Study Completion |
| Status Newborn (The gender, APGAR score, height, weight and head circumference, physical examination and any malformations of the newborn(s) will be recorded.) |
After delivery (about 9 months after IVF) |
|
|
Target Sample Size
|
Total Sample Size="1066"
Sample Size from India="212"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3/ Phase 4 |
|
Date of First Enrollment (India)
|
15/01/2016 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
17/08/2015 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="11"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
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). |