Lutropin Alfa in Women at Risk of Poor Response

July 30, 2018 updated by: Merck KGaA, Darmstadt, Germany

Lutropin Alfa (Luveris®) in Women at Risk of Poor Response Suppressed With Cetrorelix: an Exploratory Trial

Evaluate the effectiveness of adding lutropin alfa (recombinant human luteinizing hormone [r-hLH]) in the middle of the follicular phase compared to no addition, in infertile women at risk of poor response stimulated with follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) under Gonadotropin Releasing Hormone (GnRH) antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), in the number and quality of oocytes, follicular development, fertilization oocyte, embryo quality, and pregnancy rate.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
58

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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

  • Spain
      • Valencia, Spain
        • Hospital Universitario de la Fe

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 38 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Participants who were at risk of poor response by at least one of the following criteria: a) <3 follicles in last cycle, or less than or equal to (</=) 2 metaphase II oocytes, or estradiol (E2) <600 pg/mL; b) Cancellation of previous cycle; c) Early follicular serum Follicle-Stimulating Hormone (FSH) >8.5 milli IU/L
  • Participants with normal baseline luteinizing hormone and E2 levels
  • Regular menstrual cycles of 25-35 days
  • Presence of both ovaries and uterus able to withstand pregnancy

Exclusion Criteria:

  • Participants who had any clinically significant disease including known human immunodeficiency virus (HIV), hepatitis-B virus (HBV)/hepatitis-C virus (HCV) positivity
  • Participants with more than 3 previous assisted reproductive techniques (ART) cycles
  • Participants with polycystic ovaries or cyst of unknown etiology; unexplained gynecological bleeding
  • Participants who had any contraindication to being pregnant
  • Active substance abuse
  • Participants who had simultaneously participated in another clinical drug trial

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: r-FSH + r-hLH
Lutropin alfa (r-hLH) will be administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) will be administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist.
Drug: r-FSH
r-FSH will be administered as specified in the arm description.
Other Names:
  • Follitropin alfa; Gonal-F®
Drug: r-hLH
r-hLH will be administered as specified in the arm description.
Other Names:
  • Lutropin alfa; Luveris®
Drug: Analogous GnRH antagonist
Analogous GnRH antagonist will be administered as specified in the arm description.
Other Names:
  • Cetrotide®
Drug: r-hCG
r-hCG will be administered as specified in the arm description.
Drug: Progesterone
Progesterone will be administered as specified in the arm description.
ACTIVE_COMPARATOR: r-FSH
Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG will be administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist.
Drug: r-FSH
r-FSH will be administered as specified in the arm description.
Other Names:
  • Follitropin alfa; Gonal-F®
Drug: Analogous GnRH antagonist
Analogous GnRH antagonist will be administered as specified in the arm description.
Other Names:
  • Cetrotide®
Drug: r-hCG
r-hCG will be administered as specified in the arm description.
Drug: Progesterone
Progesterone will be administered as specified in the arm description.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Oocytes Retrieved
Time Frame: At the end of stimulation (Day 2 up to Day 8)
At the end of stimulation (Day 2 up to Day 8)
Number of Follicles Greater Than (>) 14 Millimeter (mm) in Diameter
Time Frame: At the end of stimulation (Day 2 up to Day 8)
At the end of stimulation (Day 2 up to Day 8)
Oocytes Recovery Rate
Time Frame: At the end of stimulation (Day 2 up to Day 8)
Oocytes recovery rate (oocytes per >14 mm follicle) is defined as number of oocytes retrieved divided by number of follicles >14 mm in diameter.
At the end of stimulation (Day 2 up to Day 8)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Oocyte Nuclear Maturity Rate
Time Frame: At the end of stimulation (Day 2 up to Day 8)
Oocyte nuclear maturity rate (metaphase II oocytes per retrieved oocyte) is defined as number of metaphase II oocytes divided by total number of oocytes retrieved.
At the end of stimulation (Day 2 up to Day 8)
Fertilization Rate
Time Frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
The fertilization rate (2 pronuclei [PN] fertilized oocytes per inseminated oocyte) was defined as number of 2 PN fertilized oocytes divided by number of inseminated oocytes.
Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Embryos by Quality
Time Frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Embryo quality was graded according to morphological classification of Veeck. Grade 1: even blastomeres with no fragmentation; Grade 2: even blastomeres with slight fragmentation (less than 20%); Grade 3: uneven size blastomeres with no fragmentation; Grade 4: even or uneven size blastomeres with moderate fragmentation (20-25%); and Grade 5: unrecognizable blastomeres with severe fragmentation (>50%).
Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Embryos Transferred by In Vitro Fertilization (IVF)
Time Frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Participants With Positive Pregnancy Test
Time Frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
The beta Human Chorionic Gonadotropin (beta-hCG) test was used as pregnancy test.
Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Participants With Clinical Pregnancy
Time Frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
A clinical pregnancy is a pregnancy that is confirmed by both pregnancy test (beta-hCG test) and sonographic confirmation of a gestational sac or heartbeat (fetal sac).
Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Implementation Rate
Time Frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Implementation rate (clinical pregnancy/embryo transferred) was defined as the number of clinical pregnancies divided by number of embryos transferred.
Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Plasma Level of Estradiol
Time Frame: At the time of r-hCG administration (any days between Day 2 to Day 8)
At the time of r-hCG administration (any days between Day 2 to Day 8)
Endometrial Thickness
Time Frame: At the time of r-hCG administration (any days between Day 2 to Day 8)
At the time of r-hCG administration (any days between Day 2 to Day 8)
Duration of Ovarian Stimulation
Time Frame: Randomization to Day 8
Duration of ovarian stimulation was defined as the time from start of study treatment to time of r-hCG administration.
Randomization to Day 8
rFSH Cumulative Dose
Time Frame: Randomization to Day 8
Randomization to Day 8
Plasma Levels of LH
Time Frame: At the time of r-hCG administration (any days between Day 2 to Day 8)
At the time of r-hCG administration (any days between Day 2 to Day 8)
Number of Participants in Whom At Least 1 Stimulation Cycle Was Cancelled
Time Frame: Randomization to Day 8
Randomization to Day 8

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck KGaA, Darmstadt, Germany

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

  • M.J. Fernández Ramírez, A. Monzó, T. García-Gimeno, J.M. Rubio, V. Montañana, C. Duque, G. Herrero, A. Romeu. Role of LH administration during the follicullar phase in women with risk of low response in ovarian stimulation with FSH and cetrorelix for IVF, REVISTA IBEROAMERICANA DE FERTILIDAD, Vol. 23- nº 5 - Septiembre-Octubre 2006

Helpful Links

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 (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 7, 2005

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 30, 2007

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 30, 2007

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 26, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2010

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 28, 2010

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IMP26170 (INI25954)
  • 2005-002229-30 (EUDRACT_NUMBER)

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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