Unexplained InfertilityPhase 3NCT03563664
Effect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure
A Phase 3 study testing Pre-treatment endometrial biopsy, Danazol and Post-treatment endometrial biopsy in people with Unexplained Infertility, run by Ain Shams University at 1 site in Egypt.
Trial summary
This study investigates the presence of a possible link between treatment with danazol and expression of endometrial αvβ3 integrin which might allow tailoring of danazol treatment to the subset of repeated IVF/ET failure that might benefit most from it. Read more about this study
- Who is it for?
- Ages 20 to 38 years, women only
- Conditions the study is for
- Unexplained Infertility
- What is being tested?
- Pre-treatment endometrial biopsy, Danazol and Post-treatment endometrial biopsy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Aug 2015to 15 Aug 2017
- Phase
- Phase 3
- 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 20 to 38 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age: 20-38 yrs
- Unexplained recurrent implantation failure (RIF), defined as failure to achieve an intrauterine gestational sac recognized by ultrasonography after transfer of at least four good-quality embryos (defined as those with four or five blastomeres on day 2, seven or more cells on day 3, ≤ 20% anucleated fragments and absence multinucleated blastomeres) in a minimum of three fresh or frozen IVF cycles after exclusion of other causes of RIF (as depicted by normal transvaginal ultrasonography, hysteroscopy, hysterosalpingography, laparoscopic findings, male and female karyotypic examination, endocrinological profile during ovarian stimulation and negative anti-cardiolipin antibody IgM/IgG, lupus anticoagulant, thrombophilia screening (including protein C, protein S, anti thrombin III and factor V leiden) and normal male semen analysis as depicted by 2010 WHO criteria for semen analysis and sperm DNA fragmentation testing).
Who cannot join
- Anovulation
- Contraindications to treatment with danazol (including chronic liver disease, congestive heart failure, dyslipidemia or history/current thrombo-embolic disease)
- Medical comorbidities (e.g. autoimmune disorders, diabetes mellitus, etc)
- Patients who underwent induction of ovulation / received hormonal treatment during the previous three months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure - A Self-controlled Clinical Trial
This study investigates the presence of a possible link between treatment with danazol and expression of endometrial αvβ3 integrin which might allow tailoring of danazol treatment to the subset of repeated IVF/ET failure that might benefit most from it.
38 eligible ovulatory women were recruited aged 20 - 38 years with unexplained recurrent implantation failure (RIF). Timed suction endometrial biopsy was obtained from participants during the implantation window of the pretreatment cycle, followed by immunohistochemical staining for endometrial αvβ3 integrin expression, scored using H-score.
Participants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks. Post-treatment suction endometrial biopsy was obtained during the implantation window following the first ovulation after danazol treatment and endometrial αvβ3 integrin expression was compared to the pretreatment cycle.
- Conditions
- Unexplained Infertility
- Being tested
- Pre-treatment endometrial biopsy, Danazol, Post-treatment endometrial biopsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-treatment endometrial biopsyProcedure or surgery
Timed suction endometrial biopsy was obtained from participants via Wallach Endocell® 908014A endometrial cell sampler timed during the implantation window of the pretreatment cycle; followed by immunohistochemical staining using immunoperoxidase staining incorporating avidin-biotin complex (ABC) method.
DanazolDrug
Participants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks.
Post-treatment endometrial biopsyProcedure or surgery
Post-treatment suction endometrial biopsy was obtained during the implantation window following the first ovulation after danazol treatment, timed, processed and stained as described previously.
| Study group | Role | What they receive |
|---|---|---|
| Study group | Experimental | 38 ovulatory patients with unexplained recurrent implantation failure were recruited. Pre-treatment endometrial biopsy and immunohistochemical examination for endometrial αvβ3 integrin expression (using immunohistochemically stained endometrial biopsy) was done. After treatment with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks, post-treatment endometrial biopsy and immunohistochemical examination was repeated and compared with previous results. Receives: Procedure: Pre-treatment endometrial biopsy; Drug: Danazol; Procedure: Post-treatment endometrial biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
H-score
Stained sections were evaluated by the same pathologist for the intensity of brownish cytoplasmic and membranous staining of the endometrial components using the semi-quantitative scoring system originally described by Budwit-Novotny et al., H-score [6], calculated using the formula H-score=∑▒〖P_i (i+1)〗 where i is the staining intensity valued as 0, absent; 1+, weak, but detectable above control; 2+, moderate and 3+, strong; and Pi is the percentage of epithelial cells stained with each intensity (varying from 0 to 100%)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2018
- Study start1 Aug 2015
- Primary completion15 Aug 2017
- Study completion15 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unexplained InfertilityStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- 38 ovulatory patients with unexplained recurrent implantation failure were recruited. Endometrial αvβ3 integrin expression (using immunohistochemically stained endometrial biopsy) was compared before and after treatment with danazol.
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, mohammed mahmoud samy, Ain Shams University
- Investigators
- Mohamed Samy, MD, Principal investigator, M Samy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03563664
- Sponsor's protocol ID
- RIF-Danazol
- Status last verified
- Jun 2018
- First submitted
- 10 Jun 2018
- Last updated
- 21 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Danazol on Endometrial αvβ3 Integrin Expression in Patients With Unexplained Recurrent Implantation Failure - A Self-controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT03563664
- Acronym / sponsor ID
- RIF-Danazol
- Conditions
- Unexplained Infertility
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 1 Aug 2015 (actual)
- Primary completion
- 15 Aug 2017 (actual)
- Study completion
- 15 Aug 2017 (actual)
- First posted
- 20 Jun 2018 (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.
This study investigates the presence of a possible link between treatment with danazol and expression of endometrial αvβ3 integrin which might allow tailoring of danazol treatment to the subset of repeated IVF/ET failure that might benefit most from it.
38 eligible ovulatory women were recruited aged 20 - 38 years with unexplained recurrent implantation failure (RIF). Timed suction endometrial biopsy was obtained from participants during the implantation window of the pretreatment cycle, followed by immunohistochemical staining for endometrial αvβ3 integrin expression, scored using H-score.
Participants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks. Post-treatment suction endometrial biopsy was obtained during the implantation window following the first ovulation after danazol treatment and endometrial αvβ3 integrin expression was compared to the pretreatment cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 38 ovulatory patients with unexplained recurrent implantation failure were recruited. Endometrial αvβ3 integrin expression (using immunohistochemically stained endometrial biopsy) was compared before and after treatment with danazol.
| Arm | Type | Receives |
|---|---|---|
| Study group | Experimental | Procedure: Pre-treatment endometrial biopsy, Drug: Danazol, Procedure: Post-treatment endometrial biopsy38 ovulatory patients with unexplained recurrent implantation failure were recruited. Pre-treatment endometrial biopsy and immunohistochemical examination for endometrial αvβ3 integrin expression (using immunohistochemically stained endometrial biopsy) was done. After treatment with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks, post-treatment endometrial biopsy and immunohistochemical examination was repeated and compared with previous results. |
Who may qualify
- Ages
- 20 to 38 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Age: 20-38 yrs
- Unexplained recurrent implantation failure (RIF), defined as failure to achieve an intrauterine gestational sac recognized by ultrasonography after transfer of at least four good-quality embryos (defined as those with four or five blastomeres on day 2, seven or more cells on day 3, ≤ 20% anucleated fragments and absence multinucleated blastomeres) in a minimum of three fresh or frozen IVF cycles after exclusion of other causes of RIF (as depicted by normal transvaginal ultrasonography, hysteroscopy, hysterosalpingography, laparoscopic findings, male and female karyotypic examination, endocrinological profile during ovarian stimulation and negative anti-cardiolipin antibody IgM/IgG, lupus anticoagulant, thrombophilia screening (including protein C, protein S, anti thrombin III and factor V leiden) and normal male semen analysis as depicted by 2010 WHO criteria for semen analysis and sperm DNA fragmentation testing).
Key exclusion criteria (4 listed)
- Anovulation
- Contraindications to treatment with danazol (including chronic liver disease, congestive heart failure, dyslipidemia or history/current thrombo-embolic disease)
- Medical comorbidities (e.g. autoimmune disorders, diabetes mellitus, etc)
- Patients who underwent induction of ovulation / received hormonal treatment during the previous three months
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 |
|---|---|---|
| Pre-treatment endometrial biopsyTimed suction endometrial biopsy was obtained from participants via Wallach Endocell® 908014A endometrial cell sampler timed during the implantation window of the pretreatment cycle; followed by immunohistochemical staining using immunoperoxidase staining incorporating avidin-biotin complex (ABC) method. | Procedure or surgery | Study group |
| DanazolParticipants were treated with danazol (Danol® 200mg capsules, Sanofi, Guildford, UK) in daily dosage of 400 mg for 12 weeks. | Drug | Study group |
| Post-treatment endometrial biopsyPost-treatment suction endometrial biopsy was obtained during the implantation window following the first ovulation after danazol treatment, timed, processed and stained as described previously. | Procedure or surgery | Study group |
Primary outcome
H-score
Time frame: 12 weeks
Stained sections were evaluated by the same pathologist for the intensity of brownish cytoplasmic and membranous staining of the endometrial components using the semi-quantitative scoring system originally described by Budwit-Novotny et al., H-score [6], calculated using the formula H-score=∑▒〖P_i (i+1)〗 where i is the staining intensity valued as 0, absent; 1+, weak, but detectable above control; 2+, moderate and 3+, strong; and Pi is the percentage of epithelial cells stained with each intensity (varying from 0 to 100%)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2018.
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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.
Mohamed Samy, MD principal investigator
M Samy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pre-treatment endometrial biopsy, Danazol and Post-treatment endometrial biopsy in people with Unexplained Infertility, run by Ain Shams University at 1 site in Egypt.
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 2 inclusion and 4 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 21 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
H-score (time frame: 12 weeks). 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 21 Jun 2018.