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Assisted Reproductive TechniquesPhase 3PERSISTNCT01297465

PERgoveriS In Stratified Treatment for Assisted Reproductive Technique

A Phase 3 study testing Gonal-f®, Pergoveris® and Recombinant human chorionic gonadotropin (r-hCG) in people with Assisted Reproductive Techniques and Reproductive Technology, Assisted, run by Merck KGaA, Darmstadt, Germany at 23 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multicenter, multi-national, randomized, open-label comparative trial. After screening, the subjects will start down-regulation treatment on Day 21-22 of the cycle. Down-regulation treatment will start within 2 months following the screening visit. Read more about this study

Who is it for?
Ages 36 to 40 years, women only
What is being tested?
Gonal-f®, Pergoveris® and Recombinant human chorionic gonadotropin (r-hCG)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
202 participants
Where
23 sitesin 11 countries
Study dates
31 May 2011to 31 Oct 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 36 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Be a female subject justifying an in vitro fertilization and embryo transfer (IVF/ET) treatment
  • Be between her 36th and 40th birthday (both included) at the time of the randomization visit
  • Have early follicular phase (Day 2-4) serum level of basal follicle stimulating hormone (FSH less than or equal to (=<)12 IU/L) measured in the center's local laboratory during the screening period (that is within 2 months prior to down-regulation start)
  • A body mass index (BMI) less than (<) 30 kilogram per square meter (kg/m^2)
  • Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length
  • Be willing and able to comply with the protocol for the duration of the trial
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  • 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
  • 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
  • Other protocol specified inclusion criteria could also apply.

Who cannot join

  • Had >= 2 previous ART cycles with a poor response to gonadotrophin stimulation defined as =< 6 mature follicles and/or =<4 oocytes collected in any previous IVF cycle or previous cycles with a hyper response defined as >= 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
  • Had previous severe ovarian Hyperstimulation Syndrome (OHSS)
  • Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS
  • Any contraindication to being pregnant and/or carrying a pregnancy to term
  • History of 3 or more miscarriages (early or late miscarriages) due to any cause
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  • 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
  • Known allergy or hypersensitivity to human gonadotrophin preparations
  • Entered previously into this trial or simultaneous participation in another clinical trial.
  • Pregnancy and lactation period
  • Participation in another clinical trial within the past 30 days
  • Other protocol specified inclusion criteria could also apply.

Trial locations and contacts

23 sites in 11 countries.

23 sites in 11 countries

France5 sites
  • Research Site

    Bondy

  • Research Site

    Bruges

  • Research Site

    Clamart

  • Research Site

    Thenon

  • Research Site

    Villeurbanne

Other trials in France

Greece3 sites
  • Research Site

    Athens

  • Research Site

    Heraklion, Crete

  • Research Site

    Pylaia, Thessaloniki

Other trials in Greece

Italy3 sites
  • Research Site

    Bologna

  • Research Site

    Florence

  • Research Site

    Torino

Other trials in Italy

Denmark2 sites
  • Research Site

    Dronninglund

  • Research Site

    Fredericia

Other trials in Denmark

Germany2 sites
  • Research Site

    Berlin

  • Research Site

    Halle

Other trials in Germany

Russia2 sites
  • Research Site

    Moscow

  • Research Site

    Samara

Other trials in Russia

United Kingdom2 sites
  • Research Site

    London

  • Research Site

    Swansea

Other trials in United Kingdom

Finland1 site
  • Research Site

    Helsinki

Other trials in Finland

Netherlands1 site
  • Research Site

    Zwolle

Other trials in Netherlands

Poland1 site
  • Research Site

    Warsaw

Other trials in Poland

Slovakia1 site
  • Research Site

    Bratislava

Other trials in Slovakia

About this study

Official title: A Phase IIIB, Multicentre, Multinational, Randomized, Open-label Trial to Compare the Efficacy and Safety of Ovarian Stimulation With GONAL-f® Day 1 to Day 5 Followed by Pergoveris® Starting Day 6 to Pergoveris® Starting Day 1 in Women Between 36 and 40 Years of Age Undergoing Assisted Reproductive Technique (ART)

This is a multicenter, multi-national, randomized, open-label comparative trial. After screening, the subjects will start down-regulation treatment on Day 21-22 of the cycle. Down-regulation treatment will start within 2 months following the screening visit. The routine long luteal phase protocol for gonadotropin-releasing hormone (GnRH) agonist treatment will be followed. Once down-regulation has been confirmed, a pregnancy test will be performed just before randomization and start of recombinant human follicle-stimulating hormone (r-hFSH) treatment to rule out any pre-existing pregnancy. If the result is negative, the subject will be randomly assigned to one of the two treatment arms of the trial:

  • GONAL-f®: (Liquid Pen; 300 international unit [IU] of per day) stimulation Day 1-5 followed by Pergoveris® (vial/powder, 300 IU per day) from stimulation Day 6 and until required recombinant human chorionic hormone (r-hCG) criterion is met. The dose can be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.
  • Pergoveris®: (vial/powder, 300 IU per day) from stimulation Day 1 and until required r-hCG criterion is met. The dose can be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.
Read more

Randomization across the two treatment arms will be kept balanced in a 1:1 ratio. Follicular development will be monitored according to the center's standard practice by ultrasound (US) and/or estradiol (E2) levels, until the protocol r-hCG requirement is met (i.e., at least one follicle greater than or equal to [>=] 18 millimeter [mm] and two follicles >=16 mm). After this, a single injection of r-hCG will be administered in order to induce final oocyte maturation.

At a time of 34-38 hours after r-hCG administration, oocytes will be recovered vaginally under US monitoring. Oocytes will then be fertilized in vitro and embryos replaced 2-5 days after oocyte recovery. Ovum pick up (OPU), in vitro fertilization (IVF), embryo transfer (ET) and luteal support will be performed as per center's standard practice.

A post-treatment safety visit will be performed for all subjects who received r-hCG (pregnant and non- pregnant) on Day 15-20 post-hCG. For subjects who have withdrawn from treatment (i.e. after starting Pergoveris® or Gonal-f® but before hCG is given) this visit will take place 20-30 days after their first Pergoveris® or Gonal-f® treatment injection (excluding pregnancy testing).

Being tested
Gonal-f®, Pergoveris®, Recombinant human chorionic gonadotropin (r-hCG)
Keywords
Ovulation Induction, Ovarian Stimulation, Reproductive Technique, Assisted, Assisted Reproductive Technics, Assisted Reproductive Technique, Reproductive Technology, Assisted
Medical subject headings
Helping Behavior

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gonal-f®Drug

    Also called Follitropin alfa

    Gonal-f® (follitropin alfa) 300 International Unit (IU) will be administered subcutaneously once daily from stimulation day 1 (S1) to stimulation day 5 (S5).

  • Pergoveris®Drug

    Pergoveris® (follitropin alfa and lutropin alfa) 300 IU will be administered subcutaneously starting from S6 until recombinant human chorionic gonadotropin (r-hCG) administration day (at least 1 follicles >= 18 mm). The dose of Pergoveris® was adjusted based upon the participant's ovarian response and according to the site's standard practice.

  • Pergoveris®Drug

    Pergoveris® (follitropin alfa and lutropin alfa) 300 IU will be administered subcutaneously once daily from S1 until r-hCG administration day (at least 1 follicles >= 18 mm). The dose of Pergoveris® was adjusted starting from S6 based upon the participant's ovarian response and according to the site's standard practice.

  • Recombinant human chorionic gonadotropin (r-hCG)Drug

    Also called Ovidrel®, Ovitrelle®

    250 microgram of r-hCG will be administered once subcutaneously on r-hCG day (at least 1 follicles >= 18 mm).

Study groups in NCT01297465
Study groupRoleWhat they receive
Gonal-f® Plus Pergoveris®Active comparatorNot described
Receives: Drug: Gonal-f®; Drug: Pergoveris®; Drug: Recombinant human chorionic gonadotropin (r-hCG)
Pergoveris®ExperimentalNot described
Receives: Drug: Pergoveris®; Drug: Recombinant human chorionic gonadotropin (r-hCG)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Total Number of Oocytes Retrieved

    The total number of oocytes retrieved per reporting group on the day of ovum pick-up (OPU) (34-38 hours post r-hCG day) was calculated. Oocyte retrieval is a technique used in in-vitro fertilization (IVF) in order to remove oocytes from the ovary of the female participant, enabling fertilization outside the body.

    Measured: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 11 days}])

Secondary outcomes (13)
  1. Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH)

    Measured: Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days])

  2. Total Number of Stimulation Treatment Days

    Measured: Day 1 up to r-hCG day (end of stimulation cycle [approximately 11 days])

  3. Implantation Rate

    Implantation rate per reporting group was measured as the number of fetal sacs observed, divided by the number of embryos transferred multiplied by 100.

    Measured: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])

  4. Number of Fetal Sacs With Activity

    Number of fetal sacs with activity was evaluated by ultrasound scan

    Measured: Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}])

  5. Number of Fetal Hearts With Activity

    Number of fetal hearts with activity was evaluated by ultrasound scan

    Measured: Days 35-42 post r-hCG day [end of stimulation cycle {approximately 11 days}])

  6. Clinical Pregnancy Rate

    Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. Clinical pregnancy rate was reported as total clinical pregnancy rate, clinical pregnancy rate per cycle started and per embryo transfer [ET]).

    Measured: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])

  7. Number of Participants With Cancelled Cycles Due to Excessive or Insufficient Ovarian Response to Treatment

    An excessive ovarian response: greater than or equal to 25 oocytes which could put the participant at risk of OHSS; An insufficient ovarian response: defined as 3 or less follicles of greater than or equal to 12 millimeter developing following at least 7 days of treatment.

    Measured: S1 until Day 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])

  8. Biochemical Pregnancies Rate

    Biochemical pregnancy was defined as the pregnancy diagnosed only by the detection of human chorionic gonadotropin (hCG) in serum or urine and that does not develop into a clinical pregnancy. Participants with beta- hCG concentration greater than 10 international units per liter (IU/L) were considered as biochemical pregnant.

    Measured: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])

  9. Number of Participants With Multiple Pregnancies

    Multiple pregnancy was defined as the existence of more than one fetal sac with fetal heart activity.

    Measured: Days 35-42 post r-hCG day (end of stimulation cycle [approximately 11 days])

  10. Number of Participants With Early and Late Ovarian Hyper Stimulation Syndrome (OHSS)

    Ovarian Hyper Stimulation Syndrome (OHSS) is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid accumulation, hemoconcentration, and increased blood clotting. Early OHSS was defined as the onset of OHSS occurring within 9 days after oocyte retrieval and late OHSS was defined as the onset of OHSS occurring on or after day 10 from oocyte retrieval.

    Measured: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])

  11. Number of Participants With Treatment-emergent Adverse Events

    An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.

    Measured: Day 1 up to days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])

  12. Systolic and Diastolic Arterial Blood Pressure Assessments

    Measured: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])

  13. Heart Rate Assessments

    Measured: Days 15-20 post r-hCG day (end of stimulation cycle [approximately 11 days])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2011 (estimated)
  2. Study start31 May 2011
  3. Primary completion31 Oct 2012
  4. Study completion31 Oct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01297465
Sponsor's protocol ID
EMR 200061-504
Other IDs
2010-023534-23
Acronym
PERSIST
Status last verified
May 2021
First submitted
15 Feb 2011
Last updated
28 May 2021

Publications

  • H Behre, C Howles, S Longobardi. Luteinizing hormone supplementation from Day 1 versus 6 of ovarian stimulation in women aged 36-40 years: results from an open-label, randomized, multicentre, multinational trial. Human Reproduction. 2013;28(suppl 1)

  • Behre HM, Howles CM, Longobardi S; PERSIST Study Investigators. Randomized trial comparing luteinizing hormone supplementation timing strategies in older women undergoing ovarian stimulation. Reprod Biomed Online. 2015 Sep;31(3):339-46. doi: 10.1016/j.rbmo.2015.06.002. Epub 2015 Jun 15.

    PubMed 26194884

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gonal-f®, Pergoveris® and Recombinant human chorionic gonadotropin (r-hCG) in people with Assisted Reproductive Techniques and Reproductive Technology, Assisted, run by Merck KGaA, Darmstadt, Germany at 23 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in France, Greece, Italy, Denmark, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Number of Oocytes Retrieved (time frame: OPU day (34-38 hours post r-hCG day [end of stimulation cycle {approximately 11 days}])). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01297465, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2021.

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