InfertilityPhase 4NCT00829244

CONSORT Randomized Controlled Trial in Assisted Reproductive Technology

A Phase 4 study testing GONAL f® prefilled pen in people with Infertility, run by Merck KGaA, Darmstadt, Germany at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The overall objective of this trial is to compare the ovarian response in assisted reproductive technology (ART) subjects administered GONAL f® according to the 'Consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment' (CONSORT) calculator versus given a standard… Read more about this study

Who is it for?: Ages 18 to 34 years, women only
Conditions the study is for: Infertility
What is being tested?: GONAL f® prefilled pen
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 200 participants
Where: 1 siteSwitzerland
Study dates: Aug 2008to Jan 2010
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 18 to 34 years
Women only
No healthy volunteers
Adult

Who may be able to join

Female subjects justifying an in-vitro fertilization (IVF)/embryo transfer (ET) treatment
Have a male partner with semen analysis within the past 6 months prior to randomization considered adequate to proceed with regular insemination or intracytoplasmic sperm injection (ICSI) according to the center's standard practice. If these criteria are not met, the subject can only be entered if donor sperm will be used
Between her 18th and 35th birthday (35 not included) at the time of the randomization visit
Body mass index (BMI) lower than 30 kilogram per square meter (kg/m^2) where the BMI is calculated according to the formula
Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length
Have an early follicular phase (Day 2-4) serum level of basal FSH lower than or equal to 12 International Unit per Liter (IU/L) measured in the center's local laboratory during the screening period (i.e. within 2 months prior to down-regulation start)

Show all 12Show fewer

Presence of both ovaries
Normal uterine cavity, which in the investigator's opinion is compatible with pregnancy
Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to randomization
Have at least 1 wash-out cycle (defined as greater than or equal to 30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting gonadotropin releasing hormone (GnRH) agonist therapy
Willing and able to comply with the protocol for the duration of the trial
Have given written informed consent, prior to any trial-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care

Who cannot join

Have greater than or equal to 2 previous ART cycles with a poor response to gonadotrophin stimulation (defined as lower than or equal to 5 mature follicles and/or lower than or equal to 3 oocytes collected) or have greater than or equal to 2 previous ART cycles with a hyper response (defined as greater than or equal to 25 oocytes retrieved)
Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Merck Serono's Medical responsible
Have previous severe ovarian hyperstimulation syndrome (OHSS)
Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS
Presence of endometriosis requiring treatment
Uterine myoma requiring treatment

Show all 18Show fewer

Any contraindication to being pregnant and/or carrying a pregnancy to term
Extra-uterine pregnancy within the last 3 months prior to screening
History of 3 or more miscarriages (early or late miscarriages) due to any cause
Tumors of the hypothalamus and pituitary gland
Ovarian enlargement or cyst of unknown etiology
Ovarian, uterine or mammary cancer
A clinically significant systemic disease
Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner,
Abnormal gynecological bleeding of undetermined origin
Known allergy or hypersensitivity to human gonadotrophin preparations,
Any active substance abuse or history of drug medication or alcohol abuse in the past 5 years prior to the screening visit
Entered previously into this trial or simultaneous participation in another clinical trial

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

Research Site
Geneva

Other trials in Switzerland

About this study

Official title: A Phase IV Prospective, Multicenter, Randomized, Open-label Trial to Assess the Efficacy and Safety of GONAL f® at a Dose Based on Subject Baseline Characteristics Determined According to the CONSORT Calculator Compared With a Standard Dose of GONAL f® 150 IU Per Day for Ovarian Stimulation in Women Undergoing Assisted Reproductive Technology (ART)

Conditions: Infertility
Being tested: GONAL f® prefilled pen
Keywords: Infertility, Assisted reproductive technology
Medical subject headings: Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GONAL f® prefilled penDrug
Also called Follitropin alfa, Recombinant human follicle stimulating hormone (r-hFSH), GONAL-f® Prefilled Pen
GONAL f® doses starting at minimum of 112.5 IU per day and a maximum of 450 IU per day for 1 cycle only
GONAL f® prefilled penDrug
Also called Follitropin alfa, r-hFSH, GONAL-f® Prefilled Pen
GONAL f® standard treatment arm (150 IU of GONAL f® per day) up to Day 5 of stimulation after which the dose can be adjusted based upon the subject's ovarian response and according to the center's standard practice.

Study groups in NCT00829244
Study group	Role	What they receive
CONSORT Dosing	Experimental	GONAL-f® dose based on subject baseline characteristics determined according to the CONSORT calculator Receives: Drug: GONAL f® prefilled pen
Standard Dosing	Active comparator	GONAL-f® at a standard dose of 150 IU per day Receives: Drug: GONAL f® prefilled pen

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Oocytes Retrieved Per Participant
Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.
Measured: 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU)

Secondary outcomes (12)

Total GONAL-f® Dose
Measured: Start of treatment until end of stimulation cycle (approximately 28 days)
Mean GONAL-f® Daily Dose
Measured: Start of treatment until end of stimulation cycle (approximately 28 days)
Total Number of GONAL-f® Stimulation Treatment Days
Measured: Start of treatment until end of stimulation cycle (approximately 28 days)
Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment
Number of participants with cancelled cycles due to excessive or inadequate response was evaluated. An excessive response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An inadequate response: defined as 3 or less follicles of greater than or equal to 12 millimeter (mm) developing following at least 7 days of GONAL-f® treatment.
Measured: Start of treatment until Day 15-20 post-hCG
Percentage of Participants With Biochemical Pregnancies
Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum and that does not develop into a clinical pregnancy.
Measured: Start of treatment until Day 15-20 Post-hCG
Number of Participants With Fetal Sacs and Fetal Hearts
Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy.
Measured: Day 35-42 Post-hCG
Implantation Rate
Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.
Measured: Day 35-42 Post-hCG
Number of Participants With Multiple Pregnancies
Multiple pregnancy was defined as 2 or more fetal hearts with activity.
Measured: Day 35-42 Post-hCG
Serum Progesterone (P4) Levels
Measured: End of stimulation cycle (approximately 28 days)
Percentage of Participants With Clinical Pregnancy
Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG.
Measured: Day 35-42 Post-hCG
Number of Participants With OHSS
OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.
Measured: Start of treatment until Day 15-20 Post-hCG
Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome
Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up).
Measured: up to 9 month (following the end of treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2008Jan 2010

First posted26 Jan 2009 (estimated)
Study startAug 2008
Primary completionJan 2010
Study completionJan 2010

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.
Publications (1)Papers the sponsor has linked to this study.
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: 200 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00829244
Sponsor's protocol ID: 28613
Status last verified: Jan 2014
First submitted: 22 Jan 2009
Last updated: 13 Feb 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Olivennes F, Trew G, Borini A, Broekmans F, Arriagada P, Warne DW, Howles CM. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa. Reprod Biomed Online. 2015 Mar;30(3):248-57. doi: 10.1016/j.rbmo.2014.11.013. Epub 2014 Dec 15.
PubMed 25596910

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 13 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase IV Prospective, Multicenter, Randomized, Open-label Trial to Assess the Efficacy and Safety of GONAL f® at a Dose Based on Subject Baseline Characteristics Determined According to the CONSORT Calculator Compared With a Standard Dose of GONAL f® 150 IU Per Day for Ovarian Stimulation in Women Undergoing Assisted Reproductive Technology (ART)
ClinicalTrials.gov ID: NCT00829244
Acronym / sponsor ID: 28613
Conditions: Infertility
Keywords: Infertility, Assisted reproductive technology
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 200 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: Aug 2008
Primary completion: Jan 2010 (actual)
Study completion: Jan 2010 (actual)
First posted: 26 Jan 2009 (estimated)
Results: Posted 7 Sep 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
CONSORT Dosing	Experimental	Drug: GONAL f® prefilled penGONAL-f® dose based on subject baseline characteristics determined according to the CONSORT calculator
Standard Dosing	Active comparator	Drug: GONAL f® prefilled penGONAL-f® at a standard dose of 150 IU per day

Who may qualify

Ages: 18 to 34 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (12 listed)

Female subjects justifying an in-vitro fertilization (IVF)/embryo transfer (ET) treatment
Have a male partner with semen analysis within the past 6 months prior to randomization considered adequate to proceed with regular insemination or intracytoplasmic sperm injection (ICSI) according to the center's standard practice. If these criteria are not met, the subject can only be entered if donor sperm will be used
Between her 18th and 35th birthday (35 not included) at the time of the randomization visit
Body mass index (BMI) lower than 30 kilogram per square meter (kg/m^2) where the BMI is calculated according to the formula
Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length

Key exclusion criteria (18 listed)

Have greater than or equal to 2 previous ART cycles with a poor response to gonadotrophin stimulation (defined as lower than or equal to 5 mature follicles and/or lower than or equal to 3 oocytes collected) or have greater than or equal to 2 previous ART cycles with a hyper response (defined as greater than or equal to 25 oocytes retrieved)
Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Merck Serono's Medical responsible
Have previous severe ovarian hyperstimulation syndrome (OHSS)
Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS
Presence of endometriosis requiring treatment

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
GONAL f® prefilled penAlso: Follitropin alfa, Recombinant human follicle stimulating hormone (r-hFSH), GONAL-f® Prefilled PenGONAL f® doses starting at minimum of 112.5 IU per day and a maximum of 450 IU per day for 1 cycle only	Drug	CONSORT Dosing
GONAL f® prefilled penAlso: Follitropin alfa, r-hFSH, GONAL-f® Prefilled PenGONAL f® standard treatment arm (150 IU of GONAL f® per day) up to Day 5 of stimulation after which the dose can be adjusted based upon the subject's ovarian response and according to the center's standard practice.	Drug	Standard Dosing

Primary outcome

Number of Oocytes Retrieved Per Participant
Time frame: 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU)
Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.

12 secondary outcomes

Total GONAL-f® Dose
Time frame: Start of treatment until end of stimulation cycle (approximately 28 days)
Mean GONAL-f® Daily Dose
Time frame: Start of treatment until end of stimulation cycle (approximately 28 days)
Total Number of GONAL-f® Stimulation Treatment Days
Time frame: Start of treatment until end of stimulation cycle (approximately 28 days)
Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment
Time frame: Start of treatment until Day 15-20 post-hCG
Percentage of Participants With Biochemical Pregnancies
Time frame: Start of treatment until Day 15-20 Post-hCG
Number of Participants With Fetal Sacs and Fetal Hearts
Time frame: Day 35-42 Post-hCG
Implantation Rate
Time frame: Day 35-42 Post-hCG
Number of Participants With Multiple Pregnancies
Time frame: Day 35-42 Post-hCG
Serum Progesterone (P4) Levels
Time frame: End of stimulation cycle (approximately 28 days)
Percentage of Participants With Clinical Pregnancy
Time frame: Day 35-42 Post-hCG
Number of Participants With OHSS
Time frame: Start of treatment until Day 15-20 Post-hCG
Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome
Time frame: up to 9 month (following the end of treatment)

Results and safety

Results posted to the registry on 7 Sep 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GONAL-f ® CONSORT Calculator	96	82
GONAL-f ® Standard Treatment	104	83

Primary outcome: Number of Oocytes Retrieved Per Participant

Time frame: 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU). Mean (Standard Deviation). Unit: oocytes

Measure	GONAL-f ® CONSORT Calculator n = 86	GONAL-f ® Standard Treatment n = 93
Value	10.0 (5.6)	11.8 (5.3)

GONAL-f ® CONSORT Calculator vs GONAL-f ® Standard Treatment: Mean Difference (Final Values): -1.7 (95% CI -3.3 to -0.1), p = 0.037, ANOVA

Population analysed: The modified Intention-To-Treat (ITT) population included all participants randomized into trial who received at least 1 dose of GONAL-f®, and who completed primary efficacy assessment (total number of oocytes retrieved per participant following GONAL-f® stimulation and hCG injection). Participants were analyzed based on treatment they received.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events (AEs) were collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until the final treatment examination, on Day 15-20 of the post-treatment assessment period. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GONAL-f ® CONSORT Calculator	4 of 96 (4.2%)	40 of 96 (41.7%)	Not reported
GONAL-f ® Standard Treatment	3 of 104 (2.9%)	48 of 104 (46.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25596910Olivennes F, Trew G, Borini A, Broekmans F, Arriagada P, Warne DW, Howles CM. Randomized, controlled, open-label, non-inferiority study of the CONSORT algorithm for individualized dosing of follitropin alfa. Reprod Biomed Online. 2015 Mar;30(3):248-57. doi: 10.1016/j.rbmo.2014.11.013. Epub 2014 Dec 15.

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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.

Pablo Arriagada, MD study director

Merck Serono S.A., Geneva

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing GONAL f® prefilled pen in people with Infertility, run by Merck KGaA, Darmstadt, Germany at 1 site in Switzerland.

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 18 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 13 Feb 2014. 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 Switzerland. 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 7 Sep 2012). 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?

Number of Oocytes Retrieved Per Participant (time frame: 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00829244, which also lists 1 linked publication.

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 13 Feb 2014.