CONSORT Randomized Controlled Trial in Assisted Reproductive Technology

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00829244
First received: January 22, 2009
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

The overall objective of this trial is to compare the ovarian response in assisted reproductive technology (ART) subjects administered GONAL f® according to the 'Consistency in recombinant follicle stimulating hormone [r-FSH] starting doses for individualized treatment' (CONSORT) calculator versus given a standard GONAL f® dose of 150 International Unit (IU) per day.


Condition Intervention Phase
Infertility
Drug: GONAL f® prefilled pen
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV Prospective, Multicenter, Randomized, Open-label Trial to Assess the Efficacy and Safety of GONAL f® at a Dose Based on Subject Baseline Characteristics Determined According to the CONSORT Calculator Compared With a Standard Dose of GONAL f® 150 IU Per Day for Ovarian Stimulation in Women Undergoing Assisted Reproductive Technology (ART)

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Oocytes Retrieved Per Participant [ Time Frame: 34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU) ] [ Designated as safety issue: No ]
    Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.


Secondary Outcome Measures:
  • Total GONAL-f® Dose [ Time Frame: Start of treatment until end of stimulation cycle (approximately 28 days) ] [ Designated as safety issue: No ]
  • Mean GONAL-f® Daily Dose [ Time Frame: Start of treatment until end of stimulation cycle (approximately 28 days) ] [ Designated as safety issue: No ]
  • Total Number of GONAL-f® Stimulation Treatment Days [ Time Frame: Start of treatment until end of stimulation cycle (approximately 28 days) ] [ Designated as safety issue: No ]
  • Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment [ Time Frame: Start of treatment until Day 15-20 post-hCG ] [ Designated as safety issue: No ]
    Number of participants with cancelled cycles due to excessive or inadequate response was evaluated. An excessive response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An inadequate response: defined as 3 or less follicles of greater than or equal to 12 millimeter (mm) developing following at least 7 days of GONAL-f® treatment.

  • Percentage of Participants With Biochemical Pregnancies [ Time Frame: Start of treatment until Day 15-20 Post-hCG ] [ Designated as safety issue: No ]
    Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum and that does not develop into a clinical pregnancy.

  • Number of Participants With Fetal Sacs and Fetal Hearts [ Time Frame: Day 35-42 Post-hCG ] [ Designated as safety issue: No ]
    Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy.

  • Implantation Rate [ Time Frame: Day 35-42 Post-hCG ] [ Designated as safety issue: No ]
    Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.

  • Number of Participants With Multiple Pregnancies [ Time Frame: Day 35-42 Post-hCG ] [ Designated as safety issue: No ]
    Multiple pregnancy was defined as 2 or more fetal hearts with activity.

  • Serum Progesterone (P4) Levels [ Time Frame: End of stimulation cycle (approximately 28 days) ] [ Designated as safety issue: No ]
  • Percentage of Participants With Clinical Pregnancy [ Time Frame: Day 35-42 Post-hCG ] [ Designated as safety issue: No ]
    Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG.

  • Number of Participants With OHSS [ Time Frame: Start of treatment until Day 15-20 Post-hCG ] [ Designated as safety issue: Yes ]
    OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.

  • Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome [ Time Frame: up to 9 month (following the end of treatment) ] [ Designated as safety issue: No ]
    Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up).


Enrollment: 200
Study Start Date: August 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CONSORT Dosing
GONAL-f® dose based on subject baseline characteristics determined according to the CONSORT calculator
Drug: GONAL f® prefilled pen
GONAL f® doses starting at minimum of 112.5 IU per day and a maximum of 450 IU per day for 1 cycle only
Other Names:
  • Follitropin alfa
  • Recombinant human follicle stimulating hormone (r-hFSH)
  • GONAL-f® Prefilled Pen
Active Comparator: Standard Dosing
GONAL-f® at a standard dose of 150 IU per day
Drug: GONAL f® prefilled pen
GONAL f® standard treatment arm (150 IU of GONAL f® per day) up to Day 5 of stimulation after which the dose can be adjusted based upon the subject's ovarian response and according to the center's standard practice.
Other Names:
  • Follitropin alfa
  • r-hFSH
  • GONAL-f® Prefilled Pen

  Eligibility

Ages Eligible for Study:   18 Years to 34 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female subjects justifying an in-vitro fertilization (IVF)/embryo transfer (ET) treatment
  2. Have a male partner with semen analysis within the past 6 months prior to randomization considered adequate to proceed with regular insemination or intracytoplasmic sperm injection (ICSI) according to the center's standard practice. If these criteria are not met, the subject can only be entered if donor sperm will be used
  3. Between her 18th and 35th birthday (35 not included) at the time of the randomization visit
  4. Body mass index (BMI) lower than 30 kilogram per square meter (kg/m^2) where the BMI is calculated according to the formula
  5. Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length
  6. Have an early follicular phase (Day 2-4) serum level of basal FSH lower than or equal to 12 International Unit per Liter (IU/L) measured in the center's local laboratory during the screening period (i.e. within 2 months prior to down-regulation start)
  7. Presence of both ovaries
  8. Normal uterine cavity, which in the investigator's opinion is compatible with pregnancy
  9. Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to randomization
  10. Have at least 1 wash-out cycle (defined as greater than or equal to 30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting gonadotropin releasing hormone (GnRH) agonist therapy
  11. Willing and able to comply with the protocol for the duration of the trial
  12. Have given written informed consent, prior to any trial-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care

Exclusion Criteria:

  1. Have greater than or equal to 2 previous ART cycles with a poor response to gonadotrophin stimulation (defined as lower than or equal to 5 mature follicles and/or lower than or equal to 3 oocytes collected) or have greater than or equal to 2 previous ART cycles with a hyper response (defined as greater than or equal to 25 oocytes retrieved)
  2. Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Merck Serono's Medical responsible
  3. Have previous severe ovarian hyperstimulation syndrome (OHSS)
  4. Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS
  5. Presence of endometriosis requiring treatment
  6. Uterine myoma requiring treatment
  7. Any contraindication to being pregnant and/or carrying a pregnancy to term
  8. Extra-uterine pregnancy within the last 3 months prior to screening
  9. History of 3 or more miscarriages (early or late miscarriages) due to any cause
  10. Tumors of the hypothalamus and pituitary gland
  11. Ovarian enlargement or cyst of unknown etiology
  12. Ovarian, uterine or mammary cancer
  13. A clinically significant systemic disease
  14. Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner,
  15. Abnormal gynecological bleeding of undetermined origin
  16. Known allergy or hypersensitivity to human gonadotrophin preparations,
  17. Any active substance abuse or history of drug medication or alcohol abuse in the past 5 years prior to the screening visit
  18. Entered previously into this trial or simultaneous participation in another clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00829244

Locations
Switzerland
Research Site
Geneva, Switzerland
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Pablo Arriagada, MD Merck Serono S.A., Geneva
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00829244     History of Changes
Other Study ID Numbers: 28613
Study First Received: January 22, 2009
Results First Received: June 1, 2012
Last Updated: January 20, 2014
Health Authority: Australia: Human Research Ethics Committee
Chile: Comisión Nacional de Investigación Científica y Tecnológica
Chile: Instituto de Salud Pública de Chile
Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: The Regional Committee on Biomedical Research Ethics
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
France: National Consultative Ethics Committee for Health and Life Sciences
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Italy: National Monitoring Center for Clinical Trials - Ministry of Health
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Comité Ético de Investigación Clínica
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
Switzerland: Ethikkommission
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Merck KGaA:
Infertility
Assisted reproductive technology

Additional relevant MeSH terms:
Infertility
Genital Diseases, Female
Genital Diseases, Male
Follicle Stimulating Hormone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014