Infertility, FemalePhase 4NCT05362799
Different Induction Protocols in PCOS After Clomiphene Citrate Failed Pregnancy in Non-IVF Cycles
A Phase 4 study testing Letrozol (Femara, Novartis), Letrozol (Femara, Novartis) combined with Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) and highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) in people with Infertility, Female, run by Menoufia University.
Trial summary
The aim of this study will be to compare between 4 different induction protocols in women who: 1. Failed to achieve ovulation after clomiphene citrate treatment at a dose of 150mg daily (if the patient can tolerate this dose) for 5 days for 3 cycles or only 100 mg daily for the same duration (if she can't tolerate… Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility, Female
- What is being tested?
- Letrozol (Femara, Novartis), Letrozol (Femara, Novartis) combined with Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) and highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 176 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2022to 31 Dec 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Women aged between 20-35 years
- Body mass index ≤ 30
- Primary or secondary infertility for ≥1 year due to PCOS (diagnosed based on Rotterdam criteria which require the presence of two of the following: Oligo\an ovulation , hyperandrogenism, polycystic ovaries on ultrasound)
- Failure to achieve ovulation after clomiphene citrate treatment at a dose of 150mg daily (if the patient can tolerate this dose) for 5 days for 3 cycles or only 100 mg daily for the same duration (if she can't tolerate higher dose)
- Failure to achieve pregnancy after 3 cycles of ultrasound indicated ovulation with clomiphene citrate treatment at a dose of 100mg or 150mg daily.
- Day-2 follicle-stimulating hormone less than 12 IU/ml
Show all 10Show fewer
- Normal serum prolactin and thyroid function
- Normal uterine cavity
- At least one patent tube
- Male partner with normal semen count and motility according to WHO criteria
Who cannot join
- Male factor infertility
- Bilateral tubal block
- Uncontrolled thyroid dysfunction
- Uterine factor of infertility.
- Known cases with endometriosis.
About this study
The aim of this study will be to compare between 4 different induction protocols in women who:
- Failed to achieve ovulation after clomiphene citrate treatment at a dose of 150mg daily (if the patient can tolerate this dose) for 5 days for 3 cycles or only 100 mg daily for the same duration (if she can't tolerate higher dose)
- Failed to achieve pregnancy after 3 cycles of ultrasound indicated ovulation with clomiphene citrate treatment at a dose of 100mg or 150mg daily.
All induction protocols will be carried out in non-IVF cycles, and continued for 3 cycles or until pregnancy whichever will be earlier.
Read the detailed description
The study will include 4 treatment groups:
GROUP 1: Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days.
GROUP 2: Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test GROUP 3: Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry.
GROUP 4: Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test For follow up:US folliculometry will be done on Day 8 in all groups. Further appointments for folliculometry will be given upon the response. Dominant follicle will be diagnosed on Day 8 if the average follicular diameter is 12mm or more (taken in 2 perpendicular diameters) then follow up will be continued till the diameter reaching 18-22mm so that triggering ovulation will be carried out by administration of human chorionic gonadotrophins (Epifasi 5000 IU, ampoule, EIPICO pharmaceuticals, Egypt). All women will be advised to receive the injection within 12 hours of the last follicular measurement. Women will be advised to have unprotected intercourse 24-36h following hCG injection. Serum β-hCG will be measured after 2 weeks to check for pregnancy and US will be performed after 2-4 weeks from B-hCG results to confirm the presence of pregnancy.
Each couple will be involved in the study for 3 treatment cycles if pregnancy will not occur but still having the option not to continue in our study where we will manage them outside the study protocol.
Women who will get pregnant will be followed for 12w gestational age for possible detection of 1st trimester abortion.
- Conditions
- Infertility, Female
- Being tested
- Letrozol (Femara, Novartis), Letrozol (Femara, Novartis) combined with Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt), highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland), highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) combined with metformin
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Letrozol (Femara, Novartis)Drug
Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days.
Letrozol (Femara, Novartis) combined with Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt)Drug
Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test
highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland)Drug
Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry.
highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) combined with metforminDrug
Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test
| Study group | Role | What they receive |
|---|---|---|
| GROUP 1 | Active comparator | GROUP 1: Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. Receives: Drug: Letrozol (Femara, Novartis) |
| GROUP 2 | Active comparator | GROUP 2: Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test Receives: Drug: Letrozol (Femara, Novartis) combined with Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) |
| GROUP 3 | Active comparator | Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. Receives: Drug: highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) |
| GROUP 4 | Active comparator | Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test Receives: Drug: highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) combined with metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of ovulation
US detection of one or more follicles of 18mm or more
Measured: 18 month
Number of dominant follicles
US detection of follicles >18mm
Measured: 18 month
Endometrial thickness
US assessment of endometrial thickness
Measured: 18 months
Secondary outcomes (7)
Occurrence of pregnancy which will be subdivided into: chemical pregnancy or clinical pregnancy
type of pregnancy
Measured: 18 months
Total number of patients getting pregnant after each treatment cycle in each group
record occurrence of pregnancy
Measured: 18 months
Number of cycles cancelled in each group
detect cycle cancellation
Measured: 18 months
Number of patients developing OHSS in each group
detect ovarian hyperstimulation syndrom
Measured: 18 months
Number of patients having multiple pregnancy in each group
detect multiple pregnancy
Measured: 18 months
Number of patients ended by 1st trimester miscarriage in each group
detect miscarriage
Measured: 18 months
Side effects recorded in each group
record side effects that patients complaint
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2022
- Study start1 Jun 2022 (estimated)
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility, FemaleStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 176 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Menoufia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Maher, Menoufia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05362799
- Sponsor's protocol ID
- 3/2022/OBG
- Status last verified
- May 2022
- First submitted
- 2 May 2022
- Last updated
- 5 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Different Induction Protocols in PCOS After Clomiphene Citrate Failed Pregnancy in Non-IVF Cycles
- ClinicalTrials.gov ID
- NCT05362799
- Acronym / sponsor ID
- 3/2022/OBG
- Conditions
- Infertility, Female
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 176 participants (estimated)
- Lead sponsor
- Menoufia UniversityUniversity, hospital or other
- Study start
- 1 Jun 2022 (estimated)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 5 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study will be to compare between 4 different induction protocols in women who:
- Failed to achieve ovulation after clomiphene citrate treatment at a dose of 150mg daily (if the patient can tolerate this dose) for 5 days for 3 cycles or only 100 mg daily for the same duration (if she can't tolerate higher dose)
- Failed to achieve pregnancy after 3 cycles of ultrasound indicated ovulation with clomiphene citrate treatment at a dose of 100mg or 150mg daily.
All induction protocols will be carried out in non-IVF cycles, and continued for 3 cycles or until pregnancy whichever will be earlier.
Detailed description
The study will include 4 treatment groups:
GROUP 1: Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days.
GROUP 2: Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test GROUP 3: Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry.
GROUP 4: Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test For follow up:US folliculometry will be done on Day 8 in all groups. Further appointments for folliculometry will be given upon the response. Dominant follicle will be diagnosed on Day 8 if the average follicular diameter is 12mm or more (taken in 2 perpendicular diameters) then follow up will be continued till the diameter reaching 18-22mm so that triggering ovulation will be carried out by administration of human chorionic gonadotrophins (Epifasi 5000 IU, ampoule, EIPICO pharmaceuticals, Egypt). All women will be advised to receive the injection within 12 hours of the last follicular measurement. Women will be advised to have unprotected intercourse 24-36h following hCG injection. Serum β-hCG will be measured after 2 weeks to check for pregnancy and US will be performed after 2-4 weeks from B-hCG results to confirm the presence of pregnancy.
Each couple will be involved in the study for 3 treatment cycles if pregnancy will not occur but still having the option not to continue in our study where we will manage them outside the study protocol.
Women who will get pregnant will be followed for 12w gestational age for possible detection of 1st trimester abortion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GROUP 1 | Active comparator | Drug: Letrozol (Femara, Novartis)GROUP 1: Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. |
| GROUP 2 | Active comparator | Drug: Letrozol (Femara, Novartis) combined with Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt)GROUP 2: Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test |
| GROUP 3 | Active comparator | Drug: highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland)Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. |
| GROUP 4 | Active comparator | Drug: highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) combined with metforminParticipants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Women aged between 20-35 years
- Body mass index ≤ 30
- Primary or secondary infertility for ≥1 year due to PCOS (diagnosed based on Rotterdam criteria which require the presence of two of the following: Oligo\an ovulation , hyperandrogenism, polycystic ovaries on ultrasound)
- Failure to achieve ovulation after clomiphene citrate treatment at a dose of 150mg daily (if the patient can tolerate this dose) for 5 days for 3 cycles or only 100 mg daily for the same duration (if she can't tolerate higher dose)
- Failure to achieve pregnancy after 3 cycles of ultrasound indicated ovulation with clomiphene citrate treatment at a dose of 100mg or 150mg daily.
Key exclusion criteria (5 listed)
- Male factor infertility
- Bilateral tubal block
- Uncontrolled thyroid dysfunction
- Uterine factor of infertility.
- Known cases with endometriosis.
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 |
|---|---|---|
| Letrozol (Femara, Novartis)Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. | Drug | GROUP 1 |
| Letrozol (Femara, Novartis) combined with Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt)Participants of this group will receive Letrozol (Femara, Novartis) at a dose of 2.5mg twice daily starting from day 3 of the cycle for 5 days. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test | Drug | GROUP 2 |
| highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland)Participants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. | Drug | GROUP 3 |
| highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) combined with metforminParticipants of this group will receive highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland.) at a dose of 75IU S.C or IM starting from day 3 of the cycle for 5 days. Readjustment of the dose will occur upon the results of day 8 folliculometry. Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) 500 mg twice daily will also started from day 3 till the date of doing pregnancy test | Drug | GROUP 4 |
Primary outcome
Occurrence of ovulation
Time frame: 18 month
US detection of one or more follicles of 18mm or more
Number of dominant follicles
Time frame: 18 month
US detection of follicles >18mm
Endometrial thickness
Time frame: 18 months
US assessment of endometrial thickness
7 secondary outcomes
Occurrence of pregnancy which will be subdivided into: chemical pregnancy or clinical pregnancy
Time frame: 18 months
Total number of patients getting pregnant after each treatment cycle in each group
Time frame: 18 months
Number of cycles cancelled in each group
Time frame: 18 months
Number of patients developing OHSS in each group
Time frame: 18 months
Number of patients having multiple pregnancy in each group
Time frame: 18 months
Number of patients ended by 1st trimester miscarriage in each group
Time frame: 18 months
Side effects recorded in each group
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2022.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Letrozol (Femara, Novartis), Letrozol (Femara, Novartis) combined with Metformin (Cidophage 500 mg, Cid Pharmaceuticals, Egypt) and highly purified lyophilized Uroffollitropin (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) in people with Infertility, Female, run by Menoufia University.
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 10 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Occurrence of ovulation (time frame: 18 month). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 May 2022.