InfertilityPhase 4PREDICTNCT01225835
Progesterone Serum Levels in Subfertile Female Patients Undergoing in Vitro Fertilisation (IVF)
A Phase 4 study testing Menotrophin, Follitrophin alpha and Cetrorelix in people with Infertility, run by Ferring Pharmaceuticals at 8 sites in Germany.
Trial summary
This study is aimed to demonstrate that highly purified Menotrophin produces significant lower progesterone serum levels during the follicular phase in comparison to Follitropin alpha in the treatment of subfertile females undergoing an in vitro fertilisation (IVF) and to investigate if the progesterone serum levels… Read more about this study
- Who is it for?
- Ages 34 to 42 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Menotrophin, Follitrophin alpha and Cetrorelix
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 8 sitesGermany
- Study dates
- Oct 2010to Jun 2013
- Phase
- Phase 4
- 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 34 to 42 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Signed informed consent
- Subfertile premenopausal female patients eligible for in vitro fertilisation (IVF) treatment
- Aged ≥34 and ≤42 years
- Body mass index of >18 and <28 kg/m^2
- Normal pelvic ultrasound at Screening
- No more than two previous gonadotrophin stimulated cycles of IVF or intracytoplasmic sperm injection (ICSI) in the history of infertility treatment (gonadotrophin stimulated cycles not used for IVF or ICSI do not count; Clomifen cycles are no exclusion criterion)
Show all 12Show fewer
- At least 3 consecutive ovulatory menstrual cycles of 24-35 days
- No fertility stimulating drugs at all
- Sperm of partner classified as normal according to World Health Organisation (WHO) 2010 criteria
- Clinically normal baseline haematology, clinical chemistry, and urinalysis values
- Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests within the last 6 months prior to Screening
- Endocrine test results within the clinically normal limits at Screening
Who cannot join
- Presence of any clinically relevant systemic disease (e.g., insulin-dependent diabetes mellitus)
- A history of or current endocrine disease (excluding treated hypothyreosis), including polycystic ovary syndrome (PCOS) and hyperprolactinaemia
- A history of coagulation disorders
- Persistent ovarian cysts (>3 months)
- A history of hypersensitivity to any of the constituents of the study medication or related compounds
- Diagnosed poor (<3 oocytes) responders to prior gonadotrophin stimulated ART-cycle
- History of severe ovarian hyperstimulation syndrome in former gonadotrophin stimulated assisted reproductive technology (ART)-cycle
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Germany8 sites
Fertility Center Berlin
Berlin
Praxisklinik Sydow am Gendarmenmarkt
Berlin
Kinderwunschzentrum Dortmund
Dortmund
Universitätsklinikum Duesseldorf, Frauenklinik
Düsseldorf
Praxis für Kinderwunschbehandlung
Erlangen
NOVUM Zentrum
Essen
IVF Zentrum
Saar
Endokrinologikum Ulm
Ulm
About this study
Official title: Effect of Highly Purified Menotrophin and Recombinant Follicle Stimulating (rFSH, Follitrophin Alpha) in Subfertile Female Patients Undergoing IVF on Progesterone Serum Levels During the Follicular Phase and Their Possible Use as Predictors for the Success Rate of Ongoing Pregnancies
This study is aimed to demonstrate that highly purified Menotrophin produces significant lower progesterone serum levels during the follicular phase in comparison to Follitropin alpha in the treatment of subfertile females undergoing an in vitro fertilisation (IVF) and to investigate if the progesterone serum levels might be a useful predictor for the success rate of the ongoing pregnancy rates
- Conditions
- Infertility
- Being tested
- Menotrophin, Follitrophin alpha, Cetrorelix, Choriongonadotropin, Progesterone
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MenotrophinDrug
Also called Menogon® HP
Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met.
Follitrophin alphaDrug
Also called Gonal-f®
Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met.
CetrorelixDrug
Also called Cetrotide®, GnRH antagonist
Participants self-inject subcutaneously Cetrorelix in the morning at a daily dose of 0.25 mg/day from Day 5 of gonadotrophin administration on and continue throughout the period of gonadotrophin treatment up to day 12 as a maximum. The last dose of Cetrorelix is given on the day of ovulation induction.
ChoriongonadotropinDrug
Also called Brevactid®, human chorionic gonadotropin (hCG)
10,000 IU administered by the Investigator or designated personnel in the evening of the day on which the hCG criterion is met (no later than Day 13). The criterion for hCG administration is three follicles >+17 mm diameter as shown by pelvic ultrasound examination.
ProgesteroneDrug
Also called Crinone®, intravaginal progesterone
Vaginal gel progesterone is used once daily at a dose of 90 mg for a period of 30 days starting on the day of oocyte retrieval (approximately Day 14).
| Study group | Role | What they receive |
|---|---|---|
| Menotrophin | Experimental | Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. Receives: Drug: Menotrophin; Drug: Cetrorelix; Drug: Choriongonadotropin; Drug: Progesterone |
| Follitrophin Alpha | Active comparator | Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. Receives: Drug: Follitrophin alpha; Drug: Cetrorelix; Drug: Choriongonadotropin; Drug: Progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration
Ovulation induction was performed by administration of hCG once three follicles >=17 mm diameter as shown by pelvic ultrasound examination. This outcome compares the serum progesterone level the morning prior to hCG administration across treatment arm, and also by age stratum (<39 years and >=39 years).
Measured: approximately day 10
Secondary outcomes (17)
Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration
The influence of the progesterone level on the ongoing pregnancy rate (in relation to all randomized patients) was determined by means of the receiver operating characteristic (ROC) curve. Youden's Index (sensitivity + specificity -1) has a range of 0-1, with 0.5 indicating a random effect.
Measured: Day 7, approximately Day 10 (hCG Administration)
Percentage of Participants With Ongoing Pregnancy
Ongoing pregnancy is defined as having a positive foetal heart action nine or more weeks after the first positive pregnancy test.
Measured: approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test)
Number of Follicles at hCG Administration
Number of follicles >=17 mm diameter detected by pelvic ultrasound examination at day of hCG administration.
Measured: approximately day 10
Average Follicle Diameter at hCG Administration
Measured: approximately day 10
Number of Cumulus-oocyte Complexes Retrieved
Cumulus-oocyte complexes are oocytes with surrounding cumulus cells.
Measured: approximately day 12 after study start
Number of Pronuclear Oocytes
Pronuclear oocytes are fertilized oocytes.
Measured: approximately day 13 after study start
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade
The count of participants with different quality grades of pronuclear stage oocytes is offered. Pronuclear stage oocytes are categorized into seven grades (0A, 0B, 1-5) representing different patterns of pronuclear morphology, according to the German Pronuclear Morphology Study Group. 0A is the highest quality oocyte and grade 5 is the lowest quality.
Participants can have pronuclear stage oocytes of different grades and therefore are counted more than once.
Measured: approximately day 13
Number of Embryos Transferred
Mean number of embryos transferred 2-3 days following oocyte retrieval.
Measured: approximately day 14
Best Quality of an Embryo Transferred
Embryo quality was measured by the following grades:
- Grade 1: Evenly sized cells, regular cleavage, no fragmentation
- Grade 2: Regular or slightly irregular cleavage, <=20% fragmentation
- Grade 2.5: Regular or slightly irregular cleavage, >20%and <=50% fragmentation
- Grade 3: Irregular cleavage, >50% fragmentation, >1 intact cell
- Grade 4: Extensive fragmentation, only 1 cell intact
- Grade 5: Totally fragmented, no viable cells.
Grade 1 represents the healthiest embryos and Grade 5 embryos are not viable.
Measured: approximately day 14
Number of Frozen Oocytes at Pronuclear Stage
No more than three normally developed embryos were transferred 2-3 days after oocyte retrieval. Other normally developed embryos were frozen.
Measured: approximately day 14
Endometrial Thickness on Day of hCG Administration
Endometrial thickness was assessed by pelvic ultrasound on the day of hCG administration.
Measured: approximately day 10
Estradiol (E2) Levels on Day of hCG Administration
Measured: approximately day 10
Percentage of Participants With Successful Embryo Transfer
Measured: approximately day 18
Number of Days Stimulated With Gonadotrophins
Number of days in which gonadotrophins were administered until hCG criteria were met. If hCG criteria were not met by day 13, the participant was withdrawn from the study.
Measured: Day 1 up to Day 12
Number of Ampoules of Gonadotrophins Used
Number of ampoules of gonadotrophins used with the goal of reaching hCG criteria. Each ampoule contained 75 IU of either menotrophin or follitrophin alpha.
Measured: Day 1 up to Day 12
Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test
A pelvic ultrasound scan was performed approximately 6 weeks after the first positive pregnancy test and the presence of an active foetal heart action indicated a clinical pregnancy.
Measured: approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test
Summary of Pregnancy Outcome
Pregnancy outcomes were reported at the optional long-term follow up visit.
Measured: up to 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionJan 2013
- Study completionJun 2013
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.
- Other trials for 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ferring Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ferring Arzneimittel GmbH
- Responsible party
- Sponsor
- Investigators
- Clinical Development Support, Study director, Ferring Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01225835
- Sponsor's protocol ID
- FE999906 CS11
- Other IDs
- 2010-019411-37
- Acronym
- PREDICT
- Status last verified
- Feb 2014
- First submitted
- 7 Oct 2010
- Last updated
- 14 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Highly Purified Menotrophin and Recombinant Follicle Stimulating (rFSH, Follitrophin Alpha) in Subfertile Female Patients Undergoing IVF on Progesterone Serum Levels During the Follicular Phase and Their Possible Use as Predictors for the Success Rate of Ongoing Pregnancies
- ClinicalTrials.gov ID
- NCT01225835
- Acronym / sponsor ID
- PREDICT / FE999906 CS11
- Conditions
- Infertility
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Ferring PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Ferring Arzneimittel GmbH
- Study start
- Oct 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 21 Oct 2010 (estimated)
- Results
- Posted 11 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is aimed to demonstrate that highly purified Menotrophin produces significant lower progesterone serum levels during the follicular phase in comparison to Follitropin alpha in the treatment of subfertile females undergoing an in vitro fertilisation (IVF) and to investigate if the progesterone serum levels might be a useful predictor for the success rate of the ongoing pregnancy rates
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Menotrophin | Experimental | Drug: Menotrophin, Drug: Cetrorelix, Drug: Choriongonadotropin, Drug: ProgesteroneStarting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. |
| Follitrophin Alpha | Active comparator | Drug: Follitrophin alpha, Drug: Cetrorelix, Drug: Choriongonadotropin, Drug: ProgesteroneStarting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. |
Who may qualify
- Ages
- 34 to 42 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Signed informed consent
- Subfertile premenopausal female patients eligible for in vitro fertilisation (IVF) treatment
- Aged ≥34 and ≤42 years
- Body mass index of >18 and <28 kg/m^2
- Normal pelvic ultrasound at Screening
Key exclusion criteria (7 listed)
- Presence of any clinically relevant systemic disease (e.g., insulin-dependent diabetes mellitus)
- A history of or current endocrine disease (excluding treated hypothyreosis), including polycystic ovary syndrome (PCOS) and hyperprolactinaemia
- A history of coagulation disorders
- Persistent ovarian cysts (>3 months)
- A history of hypersensitivity to any of the constituents of the study medication or related compounds
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 |
|---|---|---|
| MenotrophinAlso: Menogon® HPStarting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. | Drug | Menotrophin |
| Follitrophin alphaAlso: Gonal-f®Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. | Drug | Follitrophin Alpha |
| CetrorelixAlso: Cetrotide®, GnRH antagonistParticipants self-inject subcutaneously Cetrorelix in the morning at a daily dose of 0.25 mg/day from Day 5 of gonadotrophin administration on and continue throughout the period of gonadotrophin treatment up to day 12 as a maximum. The last dose of Cetrorelix is given on the day of ovulation induction. | Drug | Follitrophin Alpha, Menotrophin |
| ChoriongonadotropinAlso: Brevactid®, human chorionic gonadotropin (hCG)10,000 IU administered by the Investigator or designated personnel in the evening of the day on which the hCG criterion is met (no later than Day 13). The criterion for hCG administration is three follicles >+17 mm diameter as shown by pelvic ultrasound examination. | Drug | Follitrophin Alpha, Menotrophin |
| ProgesteroneAlso: Crinone®, intravaginal progesteroneVaginal gel progesterone is used once daily at a dose of 90 mg for a period of 30 days starting on the day of oocyte retrieval (approximately Day 14). | Drug | Follitrophin Alpha, Menotrophin |
Primary outcome
Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration
Time frame: approximately day 10
Ovulation induction was performed by administration of hCG once three follicles >=17 mm diameter as shown by pelvic ultrasound examination. This outcome compares the serum progesterone level the morning prior to hCG administration across treatment arm, and also by age stratum (<39 years and >=39 years).
17 secondary outcomes
Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration
Time frame: Day 7, approximately Day 10 (hCG Administration)
Percentage of Participants With Ongoing Pregnancy
Time frame: approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test)
Number of Follicles at hCG Administration
Time frame: approximately day 10
Average Follicle Diameter at hCG Administration
Time frame: approximately day 10
Number of Cumulus-oocyte Complexes Retrieved
Time frame: approximately day 12 after study start
Number of Pronuclear Oocytes
Time frame: approximately day 13 after study start
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade
Time frame: approximately day 13
Number of Embryos Transferred
Time frame: approximately day 14
Best Quality of an Embryo Transferred
Time frame: approximately day 14
Number of Frozen Oocytes at Pronuclear Stage
Time frame: approximately day 14
Endometrial Thickness on Day of hCG Administration
Time frame: approximately day 10
Estradiol (E2) Levels on Day of hCG Administration
Time frame: approximately day 10
Percentage of Participants With Successful Embryo Transfer
Time frame: approximately day 18
Number of Days Stimulated With Gonadotrophins
Time frame: Day 1 up to Day 12
Number of Ampoules of Gonadotrophins Used
Time frame: Day 1 up to Day 12
Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test
Time frame: approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test
Summary of Pregnancy Outcome
Time frame: up to 10 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Clinical Development Support study director
Ferring Pharmaceuticals
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Menotrophin, Follitrophin alpha and Cetrorelix in people with Infertility, run by Ferring Pharmaceuticals at 8 sites in Germany.
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 12 inclusion and 7 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 14 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany. 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 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?
Yes. Results are posted in the registry (first posted 11 Feb 2014). 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?
Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration (time frame: approximately day 10). 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 14 Mar 2014.