Cetrotide Treatment Optimization

NCT00866034 | Terminated Phase 4 Results DMC

• 3 other identifiers: CETRO TrialCCMO: NL23973.041.08METC: 08-262/G-K
• Study Type: interventional
• Target: 617
• Locations: 1 country
• Sites: 1

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

Keywords

Cetrotide; IVF; ICSI; Treatment protocol

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (1)

• Cumulative Ongoing Pregnancy Rate

  2 years

Other Outcomes (1)

• Endocrine Profile in the Early, Mid and Late Follicular Phase.

  2 years

Study Arms (2)

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.

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.

Drug: Cetrotide (Ovarian stimulation)

Interventions

Cetrotide (Ovarian stimulation) DRUG

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

Also known as: Gonal-F, Cetrorelix

CD2

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Bart CJM Fauser: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 24929258 DERIVED

• 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.

  PMID: 24129613 DERIVED

• 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.

  PMID: 23809501 DERIVED

MeSH Terms

Interventions

cetrorelix; Ovulation Induction; follitropin alfa

Intervention Hierarchy (Ancestors)

Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques

Limitations and Caveats

The study was terminated prematurely because no significant difference was observed in clinical outcome after 617 inclusions. A much larger population would be needed to detect a small significant difference in favour of either study arm.

Results Point of Contact

• Title: Ouijdane Hamdine, MD
• Organization: UMC Utrecht

O.Hamdine@umcutrecht.nl

+31-88-7557524

Study Officials

• Nick S Macklon, Prof, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Reproductive Medicine and Gynecology

Study Record Dates

• First Submitted: March 19, 2009
• First Posted: March 20, 2009
• Study Start: February 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: March 19, 2014
• Results First Posted: December 17, 2013

Record last verified: 2014-02

Locations

NL (1)