E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016401 |
E.1.2 | Term | Female infertility of other specified origin |
E.1.2 | System Organ Class | 100000004872 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025511 |
E.1.2 | Term | Male infertility, unspecified |
E.1.2 | System Organ Class | 100000004872 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016403 |
E.1.2 | Term | Female infertility of tubal origin |
E.1.2 | System Organ Class | 100000004872 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This project seeks to determine whether estradiol suppression achieved with adjuvant treatment with an aromatase inhibitor improves luteal phase parameters during IVF. |
Projektets formål er at undersøge om østradiol hæmning opnået ved adjuverende behandling med aromatase inhibitor under IVF forbedrer parametrene af den luteale fase. |
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E.2.2 | Secondary objectives of the trial |
Oocyte fertilisation, embryo quality, implantantation, pregnancy rate |
Oocyt fertilisation, embryo kvalitet, implantation, graviditetsrate |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
EudraCT number 2015-005683-41
RIOT-B: Mapping the endocrine determinants of cycle wave secondarily recruited follicles
Primary endpoints:
1. Size of follicle cohort in relation to serum endocrine and paracrine markers including
AMH, Estradiol, FSH, LH, Testosterone, Progesterone, 17-Hydroxyprogesterone
PAPP-A and A2
Inhibin A and B
BMPs
2. Size of the cyclically recruited follicle cohort (AFC) after ovarian stimulation with and without co-treatment with AI.
3. Expression of cytokine and growth factors in endometrial secretions, uterine contractility and follicular fluid endocrine and paracrine markers following co-treatment with AI compared with placebo control.
Secondary endpoints:
Area under the curve from day 4 to day 10 post hCG administration for, P and 17-hydroxyprogesterone (17-HP).
2. Serum E2, P and T levels on Stimulation day 5, day of hCG administration (or the day before), day of oocyte pick up, day 7 and 10 after hCG administration.
3. Total IU of FSH used per cycle.
4. Number of follicles > 12 mm on day of hCG (or the day before) and oocytes obtained.
5. Proportion of oocytes resulting in top quality day 2 (or day 3) embryos according to validated morphological criteria.
6. Oocyte fertilization rate
7. Number and quality of embryos obtained.
8. Endometrial thickness on day of hCG (or the day before) and day of embryo transfer.
9. Uterine contraction rate (contractions/minute) day 3 or 4 or 5 after ovulation (determined by urine LH test) in natural cycle and just prior to embryo transfer in stimulated cycle
10. Implantation rate, biochemical and ongoing pregnancy rate (viable intra-uterine pregnancy recorded at week 7-8 ultrasound).
11. Reported side effects
12. Morphometric/kinetic markers of embryo quality
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EudraCT number 2015-005683-41
RIOT-B: Kortlæggelse af de endokrine determinanter for cyklisk sekundært rekrutterede follikler |
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E.3 | Principal inclusion criteria |
Indication for IVF/ICSI treatment
Eligible for IVF/ICSI treatment according to local criteria
IVF/ICSI treatment with single embryo transfer
Regular cycles 21-35 days (both included)
Age < 40
AMH 8- 32 (both included)
Written consent
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E.4 | Principal exclusion criteria |
Any contraindication for IVF/ICSI treatment according to local criteria
Previous stimulation for IVF/ICSI with < 4 oocytes obtained
PCOS
Undergoing IVF/ICSI for the purpose of fertility preservation
Allergy towards study drug
After inclusion the participants will be excluded from further participation in the trial in case of
Withdrawal of consent
Lack of compliance with study medication
Medical complications arising from IVF treatment that would require the cycle to be terminated on clinical grounds
Serious adverse event or reaction including severe allergy to study drug or developing an excessive response to ovarian hyperstimulation in the follicular phase for which termination of all medication was required.
Specific adverse reactions to study drug: severe degree of hot flushes, severe degree of nausea/vomiting, severe degree of muscle and joint pain.
Participants who are withdrawn from the study will be replaced by inclusion of new participants.
Should the study participant present with ovarian cyst or inadequate endometrium thickness according to local guidelines on the initial ultrasound scan, the participant will be managed according to local clinical policies. The participant can be randomized when she is considered ready to commence ovarian stimulation according to local protocols.
In case of a low response to stimulation resulting in cancellation of the cycle before oocyte retrieval, or when no embryos are available for transfer, the participant will be withdrawn from further participation. Both instances will be addressed in the report of results.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Serum progesterone level on day of hCG
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patient recruitment: November – August 2018
Data analysis: March 2018 – March 2019
Publication of results: December 2018 – March 2019
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Patient rekruttering: November 2016 – August 2018
Data analyse: August 2018 – Marts 2019
Publikation af resultater: December 2018 – Marts 2019 |
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E.5.2 | Secondary end point(s) |
1. Area under the curve from day 4 to day 10 post hCG administration for P and 17-hydroxyprogesterone (17-HP).
2. Serum E2, androstenedione and testosterone (T) levels on Stimulation day 5, on the day of hCG administration (or the day before), day of oocyte pick up (OPU), day 7 after hCG administration and day 10 after hCG.
3. Follicular fluid E2, androstenedione, T, inhibin B and AMH levels
4. Total IU of FSH used per cycle.
5. Number of follicles > 12 mm on day of hCG (or the day before) and oocytes obtained.
6. Proportion of oocytes resulting in top quality day 2 (or day 3) embryos according to validated morphological criteria.
7. Oocyte fertilization rate
8. Number and quality of embryos obtained, including rate of blastocyst formation.
9. Endometrial thickness on day of hCG (or the day before) and day of embryo transfer.
10. Implantation rate, biochemical and ongoing pregnancy rate (viable intra-uterine pregnancy recorded at week 7-8 ultrasound).
11. Reported side effects
12. Morphometric/kinetic markers of embryo quality
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patient recruitment: November 2016 – March 2018
Data analysis: March 2018 – September 2018
Publication of results: September 2018 – March 2019
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Patient rekruttering: November 2016 – Marts 2018
Data analyse: Marts 2018 – September 2018
Publikation af resultater: September 2018 – Marts 2019 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |