Clinical Trial Results:
A Randomised Study Comparing Two Different Regimens of Ovarian Stimulation Using Pergoveris and Cetrorelix for Controlled Ovarian Superovulation in Assisted Conception Treatment.
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Summary
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EudraCT number |
2009-012847-40 |
Trial protocol |
GB |
Global end of trial date |
05 Nov 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Jul 2020
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First version publication date |
29 Jul 2020
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Other versions |
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Summary report(s) |
Summary |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
Pergoveris_Cetrorelix_1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Edinburgh/NHS Lothian
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Sponsor organisation address |
47 Little France Crescent, Edinburgh, United Kingdom, EH16 4TJ
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Public contact |
Dr Joo Thong, NHS Lothian, 0131 2422446, joo.thong@nhslothian.scot.nhs.uk
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Scientific contact |
Dr Joo Thong, NHS Lothian, 0131 2422446, joo.thong@nhslothian.scot.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Nov 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Nov 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Nov 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The aim of this study is to investigate whether controlled ovarian stimulation using Pergoveris with early administration of Cetrorelix (from day 2 of period, i.e. day 1 of gonadotrophin stimulation) versus administration of cetrorelix starting on day 6 of stimulation will result in more top quality embryos.
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Protection of trial subjects |
nclusion criteria:
Healthy females aged 21-38 years old, regular menses 24-35 days, less than 3 failed IVF/ICSI cycles, both ovaries present (no previous surgery), able to understand protocol and no ovarian cysts of more than 20mm
Exclusion criteria:
PCOS, severe endmetriosis, AMH,6pmol, known history of poor ovarian response during assisted conception treatment, allergic to investigational compounds, lactation, use of depot hormonal contraceptive within 6 months or use of oral contraceptive within 8 weeks of starting treatment, hypertension (systolic.150mmHg; diastolic.90mmHG, history of alcohol/drug abuse, abnormal biochemistry/haematology at screening, administration of investigational drugs within 20 days of screening and ovarian cysts of more than 20mm.
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Background therapy |
This was a randomised pilot trial comparing two regimens of controlled ovarian stimulation. Pergoveris 150IU was used for ovarian stimulation which was started on day 2 of menstrual cycle. Cetrorelix 0.25mg was started on day 2 of menses versus day 7 of menstrual cycle (day 6 of ovarian stimulation). The dose of Pergoveris was increased if the patient had poor response (less than 4 follicles or serum oestradiol less than 500 pmol/l) on day 6 of Pergoveris administration (cycle day 7) to 225IU. If there is clinical evidence of ovarian hyperstimulation (excessive follicular response), the dose of Pergoveris was reduced to 112.5IU to reduce the risk of ovarian hyperstimulation syndrome. | ||
Evidence for comparator |
Patients were randomised to each of the study arms after recruitment. | ||
Actual start date of recruitment |
19 Oct 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 80
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Worldwide total number of subjects |
80
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EEA total number of subjects |
80
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
80
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients who were undergoing IVF treatment in the Assisted Conception Unit and satisfy the inclusion criteria were approached and recruited to the study. recruitment was carried out between 19 October 2010 to 4 September 2014. 80 women were recruited. | |||||||||
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Pre-assignment
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Screening details |
I: healthy women;21-38 yrs;regular menses 24-35 ds;<3 failed IVF/ICSI cycles;both ovaries present;understand protocol. E: PCOS;severe endometriosis;AMH < 6pmol/l;POR during IUI/IVF;allergic to IMPs; prior to COS;hypertension;alcohol/drug abuse;abnormal biochem/haematology results;IMP used in prior 20 ds, use of hormonal contraception within 2 mths | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
80 | |||||||||
Number of subjects completed |
80 | |||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cetrorelix day 2 of menses | |||||||||
Arm description |
Patients were randomised to receive Cetrorelix 0.25mg on day 2 (early administration/EA) of menses. Pergoveris rFSH/75IUrLH was used ofr ovarian stimulation and started on day 2 of menses | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Pergoveris
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Administered subcutaneously. Pergoveris 150IU FSH and 75IU LH starting day 2 of menses
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Investigational medicinal product name |
Cetrotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Administered subcutaneously. Cetrotide 0.25mg daily starting on day 2 of menses
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Investigational medicinal product name |
Ovitrelle
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Ovitrelle 0.25mg 35h before oocyte retrieval
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Arm title
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Cetrorelix day 7 | |||||||||
Arm description |
Patients were randomised to receive Cetrorelix 0.25mg on day 7 (late administration/LA) on day 7 of menses. Pergoveris rFSH/75IUrLH was used for ovarian stimulation and started on day 2 of menses | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Pergoveris
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Administered subcutaneously. Pergoveris 150IU FSH and 75IU LH starting day 2 of menses
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Investigational medicinal product name |
Cetrotide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Cetrotide 0.25mg daily starting day 6 of Pergoveris stimulation (cycle day 7)
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Investigational medicinal product name |
Ovitrelle
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Ovitrelle 0.25mg 35h before oocyte retrieval
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Baseline characteristics reporting groups
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Reporting group title |
Cetrorelix day 2 of menses
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Reporting group description |
Patients were randomised to receive Cetrorelix 0.25mg on day 2 (early administration/EA) of menses. Pergoveris rFSH/75IUrLH was used ofr ovarian stimulation and started on day 2 of menses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cetrorelix day 7
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Reporting group description |
Patients were randomised to receive Cetrorelix 0.25mg on day 7 (late administration/LA) on day 7 of menses. Pergoveris rFSH/75IUrLH was used for ovarian stimulation and started on day 2 of menses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cetrorelix day 2 of menses
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Reporting group description |
Patients were randomised to receive Cetrorelix 0.25mg on day 2 (early administration/EA) of menses. Pergoveris rFSH/75IUrLH was used ofr ovarian stimulation and started on day 2 of menses | ||
Reporting group title |
Cetrorelix day 7
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Reporting group description |
Patients were randomised to receive Cetrorelix 0.25mg on day 7 (late administration/LA) on day 7 of menses. Pergoveris rFSH/75IUrLH was used for ovarian stimulation and started on day 2 of menses | ||
Subject analysis set title |
Intention to treat
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All patients allocated to the treatment arm to which they were randomised.
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End point title |
Number of top quality embryos | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Completion of treatment.
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Statistical analysis title |
Number of top quality embryos | |||||||||
Comparison groups |
Cetrorelix day 2 of menses v Cetrorelix day 7
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.05 | |||||||||
Method |
t-test, 2-sided | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-1.7 | |||||||||
upper limit |
0.3 | |||||||||
Variability estimate |
Standard deviation
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End point title |
Number and size of follicles on day of hCG | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
35 hours before oocyte retrieval.
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Statistical analysis title |
Number and size of follicles on day of hCG | ||||||||||||||||||||||||
Comparison groups |
Cetrorelix day 2 of menses v Cetrorelix day 7
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Number of subjects included in analysis |
79
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.05 | ||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||
Confidence interval |
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End point title |
Number and quality of oocytes and transferable embyos | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day of operation and embryo transfers.
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Statistical analysis title |
Number and quality of oocytes and transferable emb | |||||||||
Comparison groups |
Cetrorelix day 2 of menses v Cetrorelix day 7
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Number of subjects included in analysis |
80
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.05 | |||||||||
Method |
t-test, 2-sided | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-3.8 | |||||||||
upper limit |
1.7 | |||||||||
Variability estimate |
Standard deviation
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End point title |
Endocrine profiles on day of hCG (LH) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
On day of ovulation trigger.
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Statistical analysis title |
Endocrine profiles on day of hCG (LH) | ||||||||||||
Comparison groups |
Cetrorelix day 2 of menses v Cetrorelix day 7
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Number of subjects included in analysis |
79
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Endocrine profiles on day of hCG (E2) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
On day of ovulation trigger.
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Statistical analysis title |
Endocrine profiles on day of hCG (E2) | ||||||||||||
Comparison groups |
Cetrorelix day 7 v Cetrorelix day 2 of menses
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Number of subjects included in analysis |
79
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-929 | ||||||||||||
upper limit |
1796 | ||||||||||||
Variability estimate |
Standard deviation
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End point title |
Endocrine profiles on day of hCG (Progesterone) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
On day of ovulation trigger.
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Statistical analysis title |
Endocrine profiles on day of hCG (Progesterone) | ||||||||||||
Comparison groups |
Cetrorelix day 7 v Cetrorelix day 2 of menses
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Number of subjects included in analysis |
78
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.1 | ||||||||||||
upper limit |
0.6 | ||||||||||||
Variability estimate |
Standard deviation
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End point title |
Prevention of premature LH surge | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Between randomisation and day 2 of treatment until ovulation trigger.
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| No statistical analyses for this end point | ||||||||||
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End point title |
Dose of r-FSH (Pergoveris) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From start of treatment to ovulation trigger.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of days of administration of Pergoveris | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Starting day 2 of menses (cycle day 2), provided no ovarian cysts greater than or equal to 2 cm, up to day when three follicles are greater than or equal to 17 mm diameter.
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| No statistical analyses for this end point | ||||||||||
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End point title |
Ovarian cyst formation | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From time of first administration to ovulation trigger.
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| No statistical analyses for this end point | ||||||||||
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End point title |
Outcome of treatment cycle and pregnancy rate | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Completion of treatment cycle. Clinical pregnancy rate after confirmation of heart beat at 7 weeks gestation.
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| No statistical analyses for this end point | ||||||||||
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End point title |
Rate of poor ovarian response | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Defined as four or less eggs retrieved at operation.
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
The adverse events refers to the study period.
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Adverse event reporting additional description |
One patient had OHSS and admitted to hospital. The patient conceived from treatment and had late OHSS. The pregnancy hormone, hCG produced endogenously, stimulates the ovaries further and late OHSS is a recognised complication of IVF treatment.
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Assessment type |
Systematic | ||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||
Dictionary version |
19
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Reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | ||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
