Back to resultsHYALOBARRIER® GEL ENDO Versus no HYALOBARRIER® GEL ENDO Following Operative Hysteroscopy for Improving Reproductive Outcome in Women With Intrauterine Pathology Wishing to Become Pregnant (AGNOHSTIC)
Primary Purpose
Infertility, Polyp Uterus, Myoma;Uterus
Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Hyalobarrier® gel endo
Sponsored by
About this trial
This is an interventional prevention trial for Infertility focused on measuring Infertility, Reproductive outcome, Hysteroscopy, Adhesion prophylaxis
Eligibility Criteria
Inclusion Criteria:
Women aged 18 to 47 years attending Belgian fertility clinics, scheduled for operative hysteroscopy for endometrial polyps, fibroids with uterine cavity deformation, uterine septa, intrauterine adhesions (IUAs) and retained products of conception, and wishing to conceive spontaneously or before fertility treatment with ovulation induction (OI), controlled ovarian stimulation (COS), intrauterine insemination (IUI) or IVF/ICSI.
Exclusion Criteria:
- Women younger than 18 years
- Women 48 years of age or older
- Women with a known allergy to HYALOBARRIER® GEL ENDO
- Women with an active infection of the genital tract proven by genital swabs for PCR (Chlamydia, gonococci) or endometrial biopsy (endometritis), not treated at the time of the pre- screening visit. Women adequately treated with proven cure (negative swabs or normal endometrial biopsy) can be included
- Subserosal fibroids (FIGO or PALM-COEIN classification type 6, 7) - leiomyomas that originate from the myometrium at the serosa of the uterus or intramural fibroids without uterine cavity deformation as documented by ultrasound, hysterography or hysteroscopy - as the sole uterine cavity abnormality identified in the screening phase.
- Women with fibroids, polyps, uterine septa or IUAs suffering from other symptoms, for instance abnormal uterine bleeding, but not wishing to conceive from 6 weeks following surgery
- Women with other Müllerian tract anomalies other than a uterine septum as the sole uterine cavity abnormality identified in the screening phase
- Women who participated in the trial but failed to conceive and who present with a recurrence of polyps, fibroids with cavity deformation, uterine septum or IUAs
- Women who refuse to give written informed consent.
Sites / Locations
- University hospital GhentRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Hyalobarrier® gel endo
No Hyalobarrier® gel endo
Arm Description
Application of Hyalobarrier® gel endo immediate after the complete hysteroscopic removal of the polyp, myoma, adhesion, uterine septum or retained products of conception + application of sterile ultrasound gel into the vagina (to blind all trial participants, fertility physicians and gynaecologists doing second-look hysteroscopy)
No application of Hyalobarrier® gel endo after the hysteroscopic removal of the polyp, myoma, adhesion, uterine septum or retained products of conception + application of sterile ultrasound gel into the vagina (to blind all trial participants, fertility physicians and gynaecologists doing second- or third-look hysteroscopy)
Outcomes
Primary Outcome Measures
Conception leading to live birth
the amount of clinical pregnancies at 30 weeks after randomisation, leading to live birth (at least one live foetus after 20 weeks of gestation, that resulted in at least one live baby (the investigators counted the delivery of singleton, twin or multiple pregnancies as one live birth)
Secondary Outcome Measures
Time to conception
the time from receiving the allocated treatment to the date of conception
Clinical pregnancy
An ultrasound visible gestational sac
Miscarriage
a spontaneous loss of pregnancy before 20 completed weeks of gestational age, or if gestational age is unknown, the loss of an embryo/fetus of less than 400 grams
Ectopic pregnancy
a pregnancy in which implantation takes place outside the uterine cavity
Adhesions
The severity will be scored according to the revised American Fertility Society (AFS) scoring system
Pre-eclampsia
Pre-eclampsia in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Preterm birth
Preterm birth in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Stilbirth
Stillbirth in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Low/very low birth weight (gram)
low/very low birth weight (gram) in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Caesarean section rates
caesarean section rates in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Neonatal complications
Neonatal complications in women who conceived during the study period,
The total hospital bill
Direct health-related costs
Full Information
NCT ID
NCT03880435
First Posted
March 12, 2019
Last Updated
December 15, 2022
Sponsor
University Hospital, Ghent
Collaborators
Belgium Health Care Knowledge Centre, Nordic Pharma SAS, Universitaire Ziekenhuizen KU Leuven, Universitair Ziekenhuis Brussel, Health, Innovation and Research Institute (HIRUZ) UZ Ghent, University of Liege, UCL Bruxelles, Jessa hospital, Hasselt
1. Study Identification
Unique Protocol Identification Number
NCT03880435
Brief Title
HYALOBARRIER® GEL ENDO Versus no HYALOBARRIER® GEL ENDO Following Operative Hysteroscopy for Improving Reproductive Outcome in Women With Intrauterine Pathology Wishing to Become Pregnant
Acronym
AGNOHSTIC
Official Title
The Cost-effectiveness of Anti-adhesion Treatment With HYALOBARRIER® GEL ENDO Versus no Gel Following the Removal by Hysteroscopy of Endometrial Polyps, Fibroids With Uterine Cavity Deformation, Uterine Septa, Intrauterine Adhesions or Retained Products of Conception for Improving Reproductive Outcome in Women Wishing to Become Pregnant: a Multi-centre, Parallel Group, Superiority, Double-blind, Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2019 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
May 26, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Ghent
Collaborators
Belgium Health Care Knowledge Centre, Nordic Pharma SAS, Universitaire Ziekenhuizen KU Leuven, Universitair Ziekenhuis Brussel, Health, Innovation and Research Institute (HIRUZ) UZ Ghent, University of Liege, UCL Bruxelles, Jessa hospital, Hasselt
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To compare the costs and effects of HYALOBARRIER® GEL ENDO versus no HYALOBARRIER® GEL ENDO for increasing the chance of conception leading to live birth measured at 30 weeks after randomization in women wishing to become pregnant after surgical removal of intrauterine pathology (endometrial polyps, fibroids with uterine cavity deformation, uterine septa, IUAs or RPOC after miscarriage) by hysteroscopy as an outpatient or in hospital treatment.
Detailed Description
Design:
Multi-centre, parallel group, superiority, double-blind, randomized controlled trial. Post market study of a Medical Device class III.
Participant:
Women aged 18 to 47 years attending Belgian gynaecological departments, scheduled for operative hysteroscopy for endometrial polyps, fibroids with uterine cavity deformation, uterine septa, intrauterine adhesions (IUAs) or retained products of conception, and wishing to conceive spontaneously or before fertility treatment with ovulation induction (OI), controlled ovarian stimulation (COS), intrauterine insemination (IUI) or IVF/ICSI.
Treatment:
Application of Hyalobarrier® gel endo at time of surgery
Control:
No application of Hyalobarrier® gel endo
Follow up:
short term follow-up: 30 weeks after receiving the treatment allocation long term follow-up: 66 weeks after receiving the treatment allocation
To blind all trial participants, fertility physicians and gynaecologists doing second- or third-look hysteroscopy, 10 ml of a sterile ultrasound gel will be applied into the vagina at the end of the procedure in all women regardless of their treatment allocation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Polyp Uterus, Myoma;Uterus, Adhesion, Hysteroscopy, Uterine Septum, Retained Products of Conception
Keywords
Infertility, Reproductive outcome, Hysteroscopy, Adhesion prophylaxis
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
None of the participants will be informed of the allocated treatment by the surgeon performing the operative hysteroscopy or the personnel present in the OR. The medical record will not reveal any information whether HYALOBARRIER® GEL ENDO was applied at the end of the procedure. The REDCap software will automatically document the allocation and store all the records and the randomisations. The gynaecologist doing the operative hysteroscopy should not be the same as the fertility physician and the gynaecologist doing the second look hysteroscopy. In the exceptional case that the surgeon doing the operative hysteroscopy is the same person as the fertility physician or the gynaecologist doing the second-look hysteroscopy, blinding is assured by notification of treatment allocation if the surgeon has left the operating room.
Allocation
Randomized
Enrollment
444 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Hyalobarrier® gel endo
Arm Type
Experimental
Arm Description
Application of Hyalobarrier® gel endo immediate after the complete hysteroscopic removal of the polyp, myoma, adhesion, uterine septum or retained products of conception + application of sterile ultrasound gel into the vagina (to blind all trial participants, fertility physicians and gynaecologists doing second-look hysteroscopy)
Arm Title
No Hyalobarrier® gel endo
Arm Type
No Intervention
Arm Description
No application of Hyalobarrier® gel endo after the hysteroscopic removal of the polyp, myoma, adhesion, uterine septum or retained products of conception + application of sterile ultrasound gel into the vagina (to blind all trial participants, fertility physicians and gynaecologists doing second- or third-look hysteroscopy)
Intervention Type
Device
Intervention Name(s)
Hyalobarrier® gel endo
Intervention Description
Intra-uterine application of 10ml sterile gel containing 30mg APC. It will be administered once, peroperatively immediate after the complete hysteroscopic removal of the polyp, myoma, adhesion, uterine septum or retained products of conception
Primary Outcome Measure Information:
Title
Conception leading to live birth
Description
the amount of clinical pregnancies at 30 weeks after randomisation, leading to live birth (at least one live foetus after 20 weeks of gestation, that resulted in at least one live baby (the investigators counted the delivery of singleton, twin or multiple pregnancies as one live birth)
Time Frame
> 30 weeks after randomisation
Secondary Outcome Measure Information:
Title
Time to conception
Description
the time from receiving the allocated treatment to the date of conception
Time Frame
< 30 weeks after receiving treatment allocation
Title
Clinical pregnancy
Description
An ultrasound visible gestational sac
Time Frame
< 30 weeks after receiving treatment allocation
Title
Miscarriage
Description
a spontaneous loss of pregnancy before 20 completed weeks of gestational age, or if gestational age is unknown, the loss of an embryo/fetus of less than 400 grams
Time Frame
< 30 weeks after receiving treatment allocation
Title
Ectopic pregnancy
Description
a pregnancy in which implantation takes place outside the uterine cavity
Time Frame
< 30 weeks after receiving treatment allocation
Title
Adhesions
Description
The severity will be scored according to the revised American Fertility Society (AFS) scoring system
Time Frame
> 30w after receiving treatment allocation (in women who failed to conceive)
Title
Pre-eclampsia
Description
Pre-eclampsia in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Time Frame
> 30 weeks after receiving treatment allocation
Title
Preterm birth
Description
Preterm birth in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Time Frame
> 30 weeks after receiving treatment allocation
Title
Stilbirth
Description
Stillbirth in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Time Frame
> 30 weeks after receiving treatment allocation
Title
Low/very low birth weight (gram)
Description
low/very low birth weight (gram) in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Time Frame
> 30 weeks after receiving treatment allocation
Title
Caesarean section rates
Description
caesarean section rates in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation
Time Frame
> 30 weeks after receiving treatment allocation
Title
Neonatal complications
Description
Neonatal complications in women who conceived during the study period,
Time Frame
> 30 weeks after receiving treatment allocation
Title
The total hospital bill
Description
Direct health-related costs
Time Frame
measured at the time of diagnosis of an ongoing pregnancy by the detection at 12 weeks in a clinical pregnancy of a positive heart beat on ultrasound examination
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
47 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women aged 18 to 47 years attending Belgian fertility clinics, scheduled for operative hysteroscopy for endometrial polyps, fibroids with uterine cavity deformation, uterine septa, intrauterine adhesions (IUAs) and retained products of conception, and wishing to conceive spontaneously or before fertility treatment with ovulation induction (OI), controlled ovarian stimulation (COS), intrauterine insemination (IUI) or IVF/ICSI.
Exclusion Criteria:
Women younger than 18 years
Women 48 years of age or older
Women with a known allergy to HYALOBARRIER® GEL ENDO
Women with an active infection of the genital tract proven by genital swabs for PCR (Chlamydia, gonococci) or endometrial biopsy (endometritis), not treated at the time of the pre- screening visit. Women adequately treated with proven cure (negative swabs or normal endometrial biopsy) can be included
Subserosal fibroids (FIGO or PALM-COEIN classification type 6, 7) - leiomyomas that originate from the myometrium at the serosa of the uterus or intramural fibroids without uterine cavity deformation as documented by ultrasound, hysterography or hysteroscopy - as the sole uterine cavity abnormality identified in the screening phase.
Women with fibroids, polyps, uterine septa or IUAs suffering from other symptoms, for instance abnormal uterine bleeding, but not wishing to conceive from 6 weeks following surgery
Women with other Müllerian tract anomalies other than a uterine septum as the sole uterine cavity abnormality identified in the screening phase
Women who participated in the trial but failed to conceive and who present with a recurrence of polyps, fibroids with cavity deformation, uterine septum or IUAs
Women who refuse to give written informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eline Meireson, MSc
Phone
+32 (0)9 332 78 17
Email
eline.meireson@uzgent.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Weyers, MD,PhD
Organizational Affiliation
Women's Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
University hospital Ghent
City
Ghent
State/Province
East-Flanders
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eline Meireson, Msc
Phone
003293327817
Email
eline.meireson@uzgent.be
12. IPD Sharing Statement
Citations:
PubMed Identifier
12923149
Citation
Acunzo G, Guida M, Pellicano M, Tommaselli GA, Di Spiezio Sardo A, Bifulco G, Cirillo D, Taylor A, Nappi C. Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study. Hum Reprod. 2003 Sep;18(9):1918-21. doi: 10.1093/humrep/deg368.
Results Reference
background
PubMed Identifier
26559098
Citation
Bosteels J, Weyers S, Kasius J, Broekmans FJ, Mol BW, D'Hooghe TM. Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. Cochrane Database Syst Rev. 2015 Nov 9;(11):CD011110. doi: 10.1002/14651858.CD011110.pub2.
Results Reference
background
PubMed Identifier
16603437
Citation
Casini ML, Rossi F, Agostini R, Unfer V. Effects of the position of fibroids on fertility. Gynecol Endocrinol. 2006 Feb;22(2):106-9. doi: 10.1080/09513590600604673.
Results Reference
background
PubMed Identifier
21777835
Citation
Di Spiezio Sardo A, Spinelli M, Bramante S, Scognamiglio M, Greco E, Guida M, Cela V, Nappi C. Efficacy of a polyethylene oxide-sodium carboxymethylcellulose gel in prevention of intrauterine adhesions after hysteroscopic surgery. J Minim Invasive Gynecol. 2011 Jul-Aug;18(4):462-9. doi: 10.1016/j.jmig.2011.04.007.
Results Reference
background
PubMed Identifier
20540664
Citation
Farhi J, Orvieto R. Cumulative clinical pregnancy rates after COH and IUI in subfertile couples. Gynecol Endocrinol. 2010 Jul;26(7):500-4. doi: 10.3109/09513590903367036.
Results Reference
background
PubMed Identifier
17636653
Citation
Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P. Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD001122. doi: 10.1002/14651858.CD001122.pub3.
Results Reference
background
PubMed Identifier
12923157
Citation
Gnoth C, Godehardt D, Godehardt E, Frank-Herrmann P, Freundl G. Time to pregnancy: results of the German prospective study and impact on the management of infertility. Hum Reprod. 2003 Sep;18(9):1959-66. doi: 10.1093/humrep/deg366.
Results Reference
background
PubMed Identifier
15105384
Citation
Guida M, Acunzo G, Di Spiezio Sardo A, Bifulco G, Piccoli R, Pellicano M, Cerrota G, Cirillo D, Nappi C. Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study. Hum Reprod. 2004 Jun;19(6):1461-4. doi: 10.1093/humrep/deh238. Epub 2004 Apr 22.
Results Reference
background
PubMed Identifier
10908775
Citation
Jansen FW, Vredevoogd CB, van Ulzen K, Hermans J, Trimbos JB, Trimbos-Kemper TC. Complications of hysteroscopy: a prospective, multicenter study. Obstet Gynecol. 2000 Aug;96(2):266-70. doi: 10.1016/s0029-7844(00)00865-6.
Results Reference
background
PubMed Identifier
21310749
Citation
Kasius JC, Broekmans FJ, Veersema S, Eijkemans MJ, van Santbrink EJ, Devroey P, Fauser BC, Fatemi HM. Observer agreement in the evaluation of the uterine cavity by hysteroscopy prior to in vitro fertilization. Hum Reprod. 2011 Apr;26(4):801-7. doi: 10.1093/humrep/der003. Epub 2011 Feb 9.
Results Reference
background
PubMed Identifier
26783243
Citation
McLernon DJ, Maheshwari A, Lee AJ, Bhattacharya S. Cumulative live birth rates after one or more complete cycles of IVF: a population-based study of linked cycle data from 178,898 women. Hum Reprod. 2016 Mar;31(3):572-81. doi: 10.1093/humrep/dev336. Epub 2016 Jan 18.
Results Reference
background
PubMed Identifier
15760959
Citation
Perez-Medina T, Bajo-Arenas J, Salazar F, Redondo T, Sanfrutos L, Alvarez P, Engels V. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study. Hum Reprod. 2005 Jun;20(6):1632-5. doi: 10.1093/humrep/deh822. Epub 2005 Mar 10.
Results Reference
background
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HYALOBARRIER® GEL ENDO Versus no HYALOBARRIER® GEL ENDO Following Operative Hysteroscopy for Improving Reproductive Outcome in Women With Intrauterine Pathology Wishing to Become Pregnant
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