In Vitro FertilizationPhase 4NCT00866034
Cetrotide Treatment Optimization
A Phase 4 study testing Cetrotide (Ovarian stimulation) in people with In Vitro Fertilization and Intracytoplasmic Sperm Injection, run by Bart CJM Fauser at 1 site in Netherlands.
Trial summary
Rationale: In daily practice fertility treatment is increasingly patient focused and innovative medication and standardized treatment guidelines are being developed to improve patient convenience. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- In Vitro Fertilization, Intracytoplasmic Sperm Injection
- What is being tested?
- Cetrotide (Ovarian stimulation)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 617 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2009to Oct 2012
- 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 39 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normo-ovulatory women < 39 years with an indication for IVF or ICSI
Who cannot join
- More than 2 previous unsuccessful IVF/ICSI cycles
- BMI > 32 kg/m2
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective, Multicenter,Randomized Controlled Trial Towards Identifying the Optimal GnRH Antagonist Treatment Protocol
Rationale:
In daily practice fertility treatment is increasingly patient focused and innovative medication and standardized treatment guidelines are being developed to improve patient convenience.
Read more
GnRH antagonist cotreatment to prevent premature luteinization during ovarian stimulation for IVF and ICSI greatly reduces the burden of treatment, partly by reducing the number of injections by around 21 compared with the optimal GnRH agonist 'long' protocol. However, the optimal GnRH antagonist protocol is still not known. There are a number of reasons to suggest that both the simplicity of treatment and clinical outcomes could be further improved by commencing GnRH antagonist treatment on the same day on which ovarian stimulation is started. These include more synchronized follicle development and reduced rates of premature luteinization. This study will investigate whether a novel early fixed start protocol improves outcomes in comparison to the widely employed late fixed start protocol.
Objective:
To demonstrate whether an early fixed start antagonist protocol improves the live birth rate compared with a late fixed start antagonist protocol by 5%.
Study design:
Prospective, multicenter, investigator sponsored, randomized controlled trial
Study population:
- Normo-ovulatory women < 39 years with an indication for IVF or ICSI
- No more than 2 previous unsuccessful IVF/ICSI cycles
- BMI ≤ 32 kg/m2
Intervention:
Two different GnRH antagonist treatment protocols used in daily practice will be compared. Patients will be randomized to receive one of the following two treatments:
- Early fixed start: start GnRH antagonist treatment with Cetrotide 0.25 mg on the same day as FSH, cycle day 2.
- Late fixed start: FSH will be administered from cycle day 2. GnRH antagonist treatment with Cetrotide 0.25 mg will commence on cycle day 6.
Main study parameters/endpoints:
The primary endpoint is the live birth rate per started cycle. A secondary endpoint is the number of embryos available for transfer.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
In addition to recording clinical outcomes, endocrine studies will be carried out at the UMC Utrecht in a sample of 200 participants who will be subjected to blood sampling at three points during the treatment cycle: prior to commencing treatment on cycle day 2, cycle day 6 and the day of hCG administration.The aim of this substudy was therefore to prospectively compare the effect of a cycle day 2 versus cycle day 6 fixed start GnRH antagonist protocol on LH, estradiol and progesterone levels in the mid and late follicular phase. In order to investigate whether the early fixed protocol exerts a significant extra burden on patients compared to the late start protocol, another group of 200 participants at the UMCU will be requested to complete the HADS questionnaire (Hospital Anxiety and Depression Scale).
- Being tested
- Cetrotide (Ovarian stimulation)
- Keywords
- Cetrotide, IVF, ICSI, Treatment protocol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cetrotide (Ovarian stimulation)Drug
Also called Gonal-F, Cetrorelix
Fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2
Cetrotide (Ovarian stimulation)Drug
Also called Gonal-F, Cetrorelix
Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6.
| Study group | Role | What they receive |
|---|---|---|
| CD2 | Experimental | Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins. Receives: Drug: Cetrotide (Ovarian stimulation) |
| CD6 | Experimental | Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2. Receives: Drug: Cetrotide (Ovarian stimulation) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live Birth Rate Per Started Cycle and Live Birth From Cryopreserved Embryos Originating From, and Occurring Within 6 Months of the Initial Treatment Cycle Will be Included in the Total Live Birth Rate Per Started Cycle.
Measured: 2 years
Secondary outcomes (1)
Cumulative Ongoing Pregnancy Rate
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2009 (estimated)
- Study startFeb 2009
- Primary completionOct 2012
- Study completionOct 2012
Why it stopped: Due to limited rate of patient inclusion
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 (3)Papers the sponsor has linked to this study.
- Other trials for In Vitro FertilizationStudies 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
- 617 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bart CJM Fauser
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Bart CJM Fauser, UMC Utrecht
- Investigators
- Nick S Macklon, Prof, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00866034
- Sponsor's protocol ID
- CETRO Trial
- Other IDs
- CCMO: NL23973.041.08, METC: 08-262/G-K
- Status last verified
- Feb 2014
- First submitted
- 19 Mar 2009
- Last updated
- 19 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hamdine O, Macklon NS, Eijkemans MJ, Laven JS, Cohlen BJ, Verhoeff A, van Dop PA, Bernardus RE, Lambalk CB, Oosterhuis GJ, Holleboom CA, van den Dool-Maasland GC, Verburg HJ, van der Heijden PF, Blankhart A, Fauser BC, Broekmans FJ; CETRO trial study group. Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. Fertil Steril. 2014 Aug;102(2):448-454.e1. doi: 10.1016/j.fertnstert.2014.05.002. Epub 2014 Jun 11.
PubMed 24929258Hamdine O, Macklon NS, Eijkemans MJ, Laven JS, Cohlen BJ, Verhoeff A, van Dop PA, Bernardus RE, Lambalk CB, Oosterhuis GJ, Holleboom CA, van den Dool-Maasland GC, Verburg HJ, van der Heijden PF, Blankhart A, Fauser BC, Broekmans FJ; CETRO trial study group. Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial. Hum Reprod. 2013 Dec;28(12):3227-35. doi: 10.1093/humrep/det374. Epub 2013 Oct 15.
PubMed 24129613Hamdine O, Broekmans FJ, Eijkemans MJ, Lambalk CB, Fauser BC, Laven JS, Macklon NS; CETRO trial study group. Early initiation of gonadotropin-releasing hormone antagonist treatment results in a more stable endocrine milieu during the mid- and late-follicular phases: a randomized controlled trial comparing gonadotropin-releasing hormone antagonist initiation on cycle day 2 or 6. Fertil Steril. 2013 Sep;100(3):867-74. doi: 10.1016/j.fertnstert.2013.05.031. Epub 2013 Jun 27.
PubMed 23809501
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Multicenter,Randomized Controlled Trial Towards Identifying the Optimal GnRH Antagonist Treatment Protocol
- ClinicalTrials.gov ID
- NCT00866034
- Acronym / sponsor ID
- CETRO Trial
- Keywords
- Cetrotide, IVF, ICSI, Treatment protocol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to limited rate of patient inclusion
- Enrolment
- 617 participants (actual)
- Lead sponsor
- Bart CJM FauserUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 20 Mar 2009 (estimated)
- Results
- Posted 17 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale:
In daily practice fertility treatment is increasingly patient focused and innovative medication and standardized treatment guidelines are being developed to improve patient convenience.
GnRH antagonist cotreatment to prevent premature luteinization during ovarian stimulation for IVF and ICSI greatly reduces the burden of treatment, partly by reducing the number of injections by around 21 compared with the optimal GnRH agonist 'long' protocol. However, the optimal GnRH antagonist protocol is still not known. There are a number of reasons to suggest that both the simplicity of treatment and clinical outcomes could be further improved by commencing GnRH antagonist treatment on the same day on which ovarian stimulation is started. These include more synchronized follicle development and reduced rates of premature luteinization. This study will investigate whether a novel early fixed start protocol improves outcomes in comparison to the widely employed late fixed start protocol.
Objective:
To demonstrate whether an early fixed start antagonist protocol improves the live birth rate compared with a late fixed start antagonist protocol by 5%.
Study design:
Prospective, multicenter, investigator sponsored, randomized controlled trial
Study population:
- Normo-ovulatory women < 39 years with an indication for IVF or ICSI
- No more than 2 previous unsuccessful IVF/ICSI cycles
- BMI ≤ 32 kg/m2
Intervention:
Two different GnRH antagonist treatment protocols used in daily practice will be compared. Patients will be randomized to receive one of the following two treatments:
- Early fixed start: start GnRH antagonist treatment with Cetrotide 0.25 mg on the same day as FSH, cycle day 2.
- Late fixed start: FSH will be administered from cycle day 2. GnRH antagonist treatment with Cetrotide 0.25 mg will commence on cycle day 6.
Main study parameters/endpoints:
The primary endpoint is the live birth rate per started cycle. A secondary endpoint is the number of embryos available for transfer.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
In addition to recording clinical outcomes, endocrine studies will be carried out at the UMC Utrecht in a sample of 200 participants who will be subjected to blood sampling at three points during the treatment cycle: prior to commencing treatment on cycle day 2, cycle day 6 and the day of hCG administration.The aim of this substudy was therefore to prospectively compare the effect of a cycle day 2 versus cycle day 6 fixed start GnRH antagonist protocol on LH, estradiol and progesterone levels in the mid and late follicular phase. In order to investigate whether the early fixed protocol exerts a significant extra burden on patients compared to the late start protocol, another group of 200 participants at the UMCU will be requested to complete the HADS questionnaire (Hospital Anxiety and Depression Scale).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD2 | Experimental | Drug: Cetrotide (Ovarian stimulation)Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins. |
| CD6 | Experimental | Drug: Cetrotide (Ovarian stimulation)Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2. |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Normo-ovulatory women < 39 years with an indication for IVF or ICSI
Key exclusion criteria (2 listed)
- More than 2 previous unsuccessful IVF/ICSI cycles
- BMI > 32 kg/m2
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 |
|---|---|---|
| Cetrotide (Ovarian stimulation)Also: Gonal-F, CetrorelixFixed start of a daily dose of 0.25mg Cetrotide on cycle day 2 | Drug | CD2 |
| Cetrotide (Ovarian stimulation)Also: Gonal-F, CetrorelixLate fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. | Drug | CD6 |
Primary outcome
Live Birth Rate Per Started Cycle and Live Birth From Cryopreserved Embryos Originating From, and Occurring Within 6 Months of the Initial Treatment Cycle Will be Included in the Total Live Birth Rate Per Started Cycle.
Time frame: 2 years
1 secondary outcome
Cumulative Ongoing Pregnancy Rate
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24929258Hamdine O, Macklon NS, Eijkemans MJ, Laven JS, Cohlen BJ, Verhoeff A, van Dop PA, Bernardus RE, Lambalk CB, Oosterhuis GJ, Holleboom CA, van den Dool-Maasland GC, Verburg HJ, van der Heijden PF, Blankhart A, Fauser BC, Broekmans FJ; CETRO trial study group. Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. Fertil Steril. 2014 Aug;102(2):448-454.e1. doi: 10.1016/j.fertnstert.2014.05.002. Epub 2014 Jun 11.
- Derived from this study: PubMed 24129613Hamdine O, Macklon NS, Eijkemans MJ, Laven JS, Cohlen BJ, Verhoeff A, van Dop PA, Bernardus RE, Lambalk CB, Oosterhuis GJ, Holleboom CA, van den Dool-Maasland GC, Verburg HJ, van der Heijden PF, Blankhart A, Fauser BC, Broekmans FJ; CETRO trial study group. Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial. Hum Reprod. 2013 Dec;28(12):3227-35. doi: 10.1093/humrep/det374. Epub 2013 Oct 15.
- Derived from this study: PubMed 23809501Hamdine O, Broekmans FJ, Eijkemans MJ, Lambalk CB, Fauser BC, Laven JS, Macklon NS; CETRO trial study group. Early initiation of gonadotropin-releasing hormone antagonist treatment results in a more stable endocrine milieu during the mid- and late-follicular phases: a randomized controlled trial comparing gonadotropin-releasing hormone antagonist initiation on cycle day 2 or 6. Fertil Steril. 2013 Sep;100(3):867-74. doi: 10.1016/j.fertnstert.2013.05.031. Epub 2013 Jun 27.
Related trials for In Vitro Fertilization
Active, not recruiting
Automation of the In Vitro Fertilization Laboratory
Infertility, ART
RecruitingPhase 4
Study of G-CSF for DOR in Patients Undergoing IVF
Diminished Ovarian Reserve, IVF
RecruitingPhase 3
Fertilo In Vitro Research Study and Trial
In Vitro Maturation of Oocytes
Not yet recruiting
Oral GnRH Antagonist (Linzagolix) Versus Injectable GnRH Antagonist in Controlled Ovarian Stimulation for In Vitro Fertilization: A Randomized Controlled Non-Inferiority Trial With a Concurrent Comparator Cohort Undergoing Progestin-Primed Ovarian Stimulation (PPOS)
Infertility, Female, Ovulation Induction
Active, not recruiting
Interest of Morphokinetic Parameters of Early Embryonic Development in the Birth Rates in Vitro Fertilization
Reproductive Disorder
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.
Nick S Macklon, Prof, PhD principal investigator
UMC Utrecht
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 Cetrotide (Ovarian stimulation) in people with In Vitro Fertilization and Intracytoplasmic Sperm Injection, run by Bart CJM Fauser at 1 site in Netherlands.
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 1 inclusion and 2 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: stopped early, as of the sponsor's last update on 19 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 1 site in Netherlands. 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 17 Dec 2013). 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?
Live Birth Rate Per Started Cycle and Live Birth From Cryopreserved Embryos Originating From, and Occurring Within 6 Months of the Initial Treatment Cycle Will be Included in the Total Live Birth Rate Per Started Cycle. (time frame: 2 years). 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 NCT00866034, which also lists 3 linked publications.
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 19 Mar 2014.