Cetrotide Treatment Optimization

February 4, 2014 updated by: Bart CJM Fauser

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.

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 Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

617

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Utrecht, Netherlands
        • University Medical Center Utrecht

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 39 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Drug: Cetrotide (Ovarian stimulation)
Fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2
Other Names:
  • Gonal-F
  • Cetrorelix
Drug: Cetrotide (Ovarian stimulation)
Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6.
Other Names:
  • Gonal-F
  • Cetrorelix
EXPERIMENTAL: 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.
Drug: Cetrotide (Ovarian stimulation)
Fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2
Other Names:
  • Gonal-F
  • Cetrorelix
Drug: Cetrotide (Ovarian stimulation)
Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6.
Other Names:
  • Gonal-F
  • Cetrorelix

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Cumulative Ongoing Pregnancy Rate
Time Frame: 2 years
2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endocrine Profile in the Early, Mid and Late Follicular Phase.
Time Frame: 2 years
  1. difference in endocrine profile between the 2 arms during the mid and late follicular phase
  2. influence of early elevated follicular phase progesterone levels on clinical outcome
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bart CJM Fauser

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (ACTUAL)

October 1, 2012

Study Completion (ACTUAL)

October 1, 2012

Study Registration Dates

First Submitted

March 19, 2009

First Submitted That Met QC Criteria

March 19, 2009

First Posted (ESTIMATE)

March 20, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

March 19, 2014

Last Update Submitted That Met QC Criteria

February 4, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CETRO Trial
  • CCMO: NL23973.041.08
  • METC: 08-262/G-K

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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