CONSORT Randomized Controlled Trial in Assisted Reproductive Technology

Infertility Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00829244
• Other study ID #: 28613
• Status: Completed
• Phase: Phase 4
• First received: January 22, 2009
• Last updated: January 20, 2014
• Start date: August 2008
• Est. completion date: January 2010

Study information

• Verified date: January 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics CommitteeChile: Comisión Nacional de Investigación Científica y TecnológicaChile: Instituto de Salud Pública de ChileDenmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: The Regional Committee on Biomedical Research EthicsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeFrance: National Consultative Ethics Committee for Health and Life SciencesGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesItaly: Ethics CommitteeItaly: National Monitoring Center for Clinical Trials - Ministry of HealthNetherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Spain: Comité Ético de Investigación ClínicaSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySweden: Regional Ethical Review BoardSwitzerland: EthikkommissionSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 34 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility

Intervention

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
• 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.

Locations

Country	Name	City	State
Switzerland	Research Site	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Oocytes Retrieved Per Participant	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.	34-38 hours post-recombinant human choriogonadotropin (hCG) (OPU)	No
Secondary	Total GONAL-f® Dose		Start of treatment until end of stimulation cycle (approximately 28 days)	No
Secondary	Mean GONAL-f® Daily Dose		Start of treatment until end of stimulation cycle (approximately 28 days)	No
Secondary	Total Number of GONAL-f® Stimulation Treatment Days		Start of treatment until end of stimulation cycle (approximately 28 days)	No
Secondary	Number of Participants With Cancelled Cycles Due to Excessive or Inadequate Response to Treatment	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.	Start of treatment until Day 15-20 post-hCG	No
Secondary	Percentage of Participants With Biochemical Pregnancies	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.	Start of treatment until Day 15-20 Post-hCG	No
Secondary	Number of Participants With Fetal Sacs and Fetal Hearts	Number of participants with fetal sacs and fetal hearts (with activity) as seen on an ultrasound scan to confirm clinical pregnancy.	Day 35-42 Post-hCG	No
Secondary	Implantation Rate	Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.	Day 35-42 Post-hCG	No
Secondary	Number of Participants With Multiple Pregnancies	Multiple pregnancy was defined as 2 or more fetal hearts with activity.	Day 35-42 Post-hCG	No
Secondary	Serum Progesterone (P4) Levels		End of stimulation cycle (approximately 28 days)	No
Secondary	Percentage of Participants With Clinical Pregnancy	Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan performed on Day 35-42 post-hCG.	Day 35-42 Post-hCG	No
Secondary	Number of Participants With OHSS	OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting.	Start of treatment until Day 15-20 Post-hCG	Yes
Secondary	Pregnancy Outcome - Number of Participants With Pregnancy and Their Outcome	Pregnancy outcomes are live outcome (live infant) and non-live outcome (non-live infant) or unknown outcome (subject lost to follow-up).	up to 9 month (following the end of treatment)	No