Cetrotide Treatment Optimization

NCT ID: NCT00866034

Last Updated: 2014-03-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 617 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2012-10-31

Brief 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.

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).

Conditions

In Vitro Fertilization; Intracytoplasmic Sperm Injection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CD2

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.

Group Type: EXPERIMENTAL

Cetrotide (Ovarian stimulation)

Intervention Type: DRUG

Fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2

CD6

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.

Group Type: EXPERIMENTAL

Cetrotide (Ovarian stimulation)

Intervention Type: DRUG

Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6.

Interventions

Cetrotide (Ovarian stimulation)

Fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2

Intervention Type: DRUG

Cetrotide (Ovarian stimulation)

Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6.

Intervention Type: DRUG

Other Intervention Names

Gonal-F; Cetrorelix; Gonal-F; Cetrorelix

Eligibility Criteria

Inclusion Criteria

• Normo-ovulatory women < 39 years with an indication for IVF or ICSI

Exclusion Criteria

• More than 2 previous unsuccessful IVF/ICSI cycles
• BMI > 32 kg/m2

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Bart CJM Fauser

OTHER

Sponsor Role: lead

Responsible Party

Bart CJM Fauser

Professor of Reproductive Medicine and Gynecology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nick S Macklon, Prof, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 24929258 (View on PubMed)

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. 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.

Reference Type: DERIVED

PMID: 24129613 (View on PubMed)

Hamdine 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.

Reference Type: DERIVED

PMID: 23809501 (View on PubMed)

Other Identifiers

CCMO: NL23973.041.08

Identifier Type: -

Identifier Source: secondary_id

METC: 08-262/G-K

Identifier Type: -

Identifier Source: secondary_id

CETRO Trial

Identifier Type: -

Identifier Source: org_study_id