CONSORT Randomized Controlled Trial in Assisted Reproductive Technology - Full Text View

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:

MedlinePlus related topics: Infertility

U.S. FDA Resources

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:

Female subjects justifying an in-vitro fertilization (IVF)/embryo transfer (ET) treatment
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
Between her 18th and 35th birthday (35 not included) at the time of the randomization visit
Body mass index (BMI) lower than 30 kilogram per square meter (kg/m^2) where the BMI is calculated according to the formula
Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length
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)
Presence of both ovaries
Normal uterine cavity, which in the investigator's opinion is compatible with pregnancy
Have a negative cervical papanicolaou (PAP) test within the last 6 months prior to randomization
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
Willing and able to comply with the protocol for the duration of the trial
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:

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)
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
Have previous severe ovarian hyperstimulation syndrome (OHSS)
Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS
Presence of endometriosis requiring treatment
Uterine myoma requiring treatment
Any contraindication to being pregnant and/or carrying a pregnancy to term
Extra-uterine pregnancy within the last 3 months prior to screening
History of 3 or more miscarriages (early or late miscarriages) due to any cause
Tumors of the hypothalamus and pituitary gland
Ovarian enlargement or cyst of unknown etiology
Ovarian, uterine or mammary cancer
A clinically significant systemic disease
Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner,
Abnormal gynecological bleeding of undetermined origin
Known allergy or hypersensitivity to human gonadotrophin preparations,
Any active substance abuse or history of drug medication or alcohol abuse in the past 5 years prior to the screening visit
Entered previously into this trial or simultaneous participation in another clinical trial

Contacts and Locations

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 21, 2013
Health Authority:	Australia: Human Research Ethics Committee Chile: Comisión Nacional de Investigación Científica y Tecnológica Chile: Instituto de Salud Publica 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, Male
Genital Diseases, Female
Follicle Stimulating Hormone

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013