Clinical Tolerance and Equivalence of hCG-IBSA vs Recombinant Human Chorionic Gonadotrophin in Women Undergoing In Vitro Fertilisation

Infertility Clinical Trial

Official title:

A Prospective, Randomized, Controlled Clinical Study on the Assessment of Tolerance and Clinical Equivalence of hCG- IBSA (IBSA) Versus Ovitrelle (Serono), Both Administered Sub-cutaneously in Women Undergoing in Vitro Fertilization (IVF).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00335569
• Other study ID #: 04CH/HCG02
• Status: Completed
• Phase: Phase 3
• First received: June 9, 2006
• Last updated: May 31, 2011
• Start date: August 2005
• Est. completion date: December 2008

Study information

• Verified date: May 2011
• Source: IBSA Institut Biochimique SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the clinical equivalence and the general tolerability of two different subcutaneous hCG preparations (hCG-IBSA, IBSA vs Ovitrelle, Serono) when administered to patients undergoing IVF.

Description:

This is a prospective, multicenter, randomized, investigator blind, parallel group, active control, phase III clinical trial. Patients meeting the eligibility requirements of the study will be randomly assigned to receive either the test drug (hCG-IBSA, IBSA) or the reference drug (Ovitrelle, Serono). Investigators will be blinded by not allowing them to have any contact with the study medications (supplied in boxes labeled in a manner that does not reveal the content of the boxes), and requesting that patients do not make any statements to the investigator that might indicate the treatment to which they were assigned. Equivalence testing with regard to the primary outcome variable will establish whether the two treatments are indeed similarly effective.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• >/=18 and < 40 years old;

• BMI between 18 and 30 kg/m2;

• less than 3 previous completed cycles;

• both ovaries present;

• regular menstrual cycle of 25-35 days;

• infertility attributable to a tubal factor, American Fertility Society grade I or II endometriosis, male factor or unexplained factor.

• within 12 months of the beginning of the study, uterine cavity consistent with expected normal function as assessed through hysterosalpingogram, sonohystrogram or hysteroscopic examination;

• basal FSH level less than 10 IU/L;

• criteria for hCG administration fulfilled (at least 2 follicles with a diameter of 16 mm or more, with acceptable serum E2 concentration).

• a male partner with semen analysis within the past 6 months showing acceptable values of seminal parameters, defined as > 3x10 exp 6 spermatozoa/ml;

• qualified to receive 150 - 300 IU FSH as starting dose.

Exclusion Criteria:

• age < 18 and > o = 40 years;

• primary ovarian failure or women known as poor responders (i.e. requiring more than 300 IU of FSH as a starting dose in previous treatment cycles or having less than 3 oocytes retrieved, or with an E2 serum concentration < 3'000 pmol/L);

• ovarian cysts > 20 mm, or enlargement not due to polycystic ovarian syndrome;

• patients affected by pathologies associated with any contraindication of being pregnant;

• hypersensitivity to the study medication;

• any bleeding since stimulation;

• uncontrolled thyroid or adrenal dysfunction;

• neoplasias;

• severe impairment of the renal and/or hepatic functions;

• use of concomitant medication that might interfere with study evaluations (e.g. nonstudy hormonal medications, prostaglandin inhibitors, psychotropic agents);

• more than 18 days of FSH stimulation.

Study Design

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

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• hCG-IBSA

Locations

Country	Name	City	State
Switzerland	Department of Gynecology and Obstetrics Universitätfrauenklinik	Basel
Switzerland	4. Department of Gynecology and Obstetrics Frauenklinik, InselspitalEffingerstrasse 102	Bern
Switzerland	Department of Gynecology and ObstetricsUniversity Hospital	Geneve
Switzerland	3. Maternity CHUV - Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (1)

Lead Sponsor	Collaborator
IBSA Institut Biochimique SA

Country where clinical trial is conducted

Switzerland, 

References & Publications (11)

Abdalla HI, Ah-Moye M, Brinsden P, Howe DL, Okonofua F, Craft I. The effect of the dose of human chorionic gonadotropin and the type of gonadotropin stimulation on oocyte recovery rates in an in vitro fertilization program. Fertil Steril. 1987 Dec;48(6):958-63. — View Citation

Brown JB, Evans JH, Adey FD, Taft HP, Townsend L. Factors involved in the induction of fertile ovulation with human gonadotrophins. J Obstet Gynaecol Br Commonw. 1969 Apr;76(4):289-307. — View Citation

Fleischer AC. Transabdominal and transvaginal sonography of ovarian masses. Clin Obstet Gynecol. 1991 Jun;34(2):433-42. Review. — View Citation

Forest MG, David M, Lecoq A, Jeune M, Bertrans J. Kinetics of the HCG-induced steroidogenic response of the human testis. III. Studies in children of the plasma levels of testosterone and HCG: rationale for testicular stimulation test. Pediatr Res. 1980 Jun;14(6):819-24. — View Citation

GEMZELL C. INDUCTION OF OVULATION WITH HUMAN GONADOTROPINS. Recent Prog Horm Res. 1965;21:179-204. Review. — View Citation

Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989 Jun;44(6):430-40. Review. — View Citation

Hauschke D, Kieser M, Diletti E, Burke M. Sample size determination for proving equivalence based on the ratio of two means for normally distributed data. Stat Med. 1999 Jan 15;18(1):93-105. — View Citation

Johnsen SG. A study of human testicular function by the use of human menopausal gonadotrophin and of human chorionic gonadotrophin in male hypogonadotrophic eunuchoidism and infantilism. Acta Endocrinol (Copenh). 1966 Oct;53(2):315-41. — View Citation

Pierce JG, Parsons TF. Glycoprotein hormones: structure and function. Annu Rev Biochem. 1981;50:465-95. Review. — View Citation

Venturoli S, Paradisi R, Fabbri R, Magrini O, Porcu E, Flamigni C. Comparison between human urinary follicle-stimulating hormone and human menopausal gonadotropin treatment in polycystic ovary. Obstet Gynecol. 1984 Jan;63(1):6-11. — View Citation

Vermesh M, Kletzky OA. Follicle-stimulating hormone is the main determinant of follicular recruitment and development in ovulation induction with human menopausal gonadotropin. Am J Obstet Gynecol. 1987 Dec;157(6):1397-402. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total number of oocytes retrieved per patient who received hCG
Secondary	Number of patients who received hCG with at least one oocyte retrieved, 2PN fertilized oocytes,
Secondary	2PN or cleaved embryos, implantation rate per embryo transferred; Serum P and hCG concentration on the days of oocyte retrieval, on day of embryo transfer and on day 5-8 post-hCG;
Secondary	Implantation rate;Pregnancy rate.
Secondary	Adverse Events	Adverse events were monitored and collected during all the study period	from day 1 to 35 +/- 7 days after oocytes retrieval	Yes
Secondary	Incidence of moderate or severe OHSS	The incidence moderate or severe of OHSS will be assessed in both treatment groups	From the day of hCG injection until 35 +/- 7 days after oocyte retrieval	Yes