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Prospective Clinical Study of Nintedanib to Inhibit Endometrial Fibrosis to Prevent Recurrence of Uterine Adhesions

Primary Purpose

Uterine Adhesions

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Nintedanib 100 MG [Ofev]
Nintedanib 150 MG [Ofev]
Sponsored by
Sixth Affiliated Hospital, Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Uterine Adhesions focused on measuring uterine adhesions, endometrail fibrisis

Eligibility Criteria

20 Years - 38 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: 1)Clinical diagnosis of uterine adhesions; 2)Body mass index between 18-27 kg/m2; 3)Have a regular menstrual cycle of 27-35 days for at least six months; 4)Hysteroscopic diagnosis of moderate to severe uterine adhesions (AFS score >5), treated with electrodesiccation; 5)No contraindications to oral estrogen and progestin such as a history of thrombosis/breast tumor/history of abnormal liver function/migraine; 6)≥ 2 oocytes or blastocysts have been frozen. Exclusion Criteria: 1)Patients with combined ovarian cysts ≥ 20 mm in diameter, submucosal uterine fibroids or intermuscular fibroids > 30 mm in diameter, pituitary tumors, and malignant tumors of various tissues and organs; 2)Patients with clinically significant abnormalities of the uterus (endometrial polyps, uterine malformations, endometriosis) and adnexa (hydrosalpinx); 3)Repeated implantation failures, such as three consecutive transfers with ≥6 failed high-quality embryos; 4)Known malformations of the reproductive organs that are unsuitable for pregnancy; 5)Abnormal cervical cytology (TCT) findings within 1 year before the screening; 6)Severe liver or kidney impairment, heart disease, or hypertension; 7)Known previous or current history of thrombophlebitis or thromboembolic disease; 8)Any known clinically significant systemic disease (e.g., diabetes mellitus, tuberculosis, etc; 9)Known history of recurrent miscarriage; 10)Chromosomal karyotype abnormalities in either spouse; 11)Genetic disorders that make either spouse unsuitable for childbirth as specified in the Maternal and Child Health Law;12)exposure of either spouse to teratogenic amounts of radiation, toxins, and drugs; 13)Participation in another drug or medical device clinical trial within 3 months before enrollment;14)Any medical condition/combined surgery/ medication/other clinically significant abnormal laboratory tests that, in the judgment of the investigator, may affect the outcome of the trial; 15)Known refusal or inability to comply with protocol requirements for any reason (including planned clinical visits and examinations).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Nintedanib 100mg

    Nintedanib 150mg

    Arm Description

    Traditional hormone replacement (HRT) cycle medication (Tegretol 2mg bid for 20 days, followed by Darvon 10mg bid for the last 10 days) + Nintedanib 100mg bid *15 days orally.

    Traditional hormone replacement (HRT) cycle medication (Tegretol 2mg bid for 20 days, followed by Darvon 10mg bid for the last 10 days) + Nintedanib 150mg bid *15 days orally.

    Outcomes

    Primary Outcome Measures

    American Fertility Association(AFS) score (mild:1-4,moderate:5-8,severe:9-12)
    American Fertility Association(AFS) scoring performed hysteroscopically

    Secondary Outcome Measures

    Endometrial thickness
    Endometrial thickness measured by ultrasonography

    Full Information

    First Posted
    November 1, 2022
    Last Updated
    November 22, 2022
    Sponsor
    Sixth Affiliated Hospital, Sun Yat-sen University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05635071
    Brief Title
    Prospective Clinical Study of Nintedanib to Inhibit Endometrial Fibrosis to Prevent Recurrence of Uterine Adhesions
    Official Title
    Prospective Clinical Study of Nintedanib to Inhibit Endometrial Fibrosis to Prevent Recurrence of Uterine Adhesions
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 1, 2023 (Anticipated)
    Primary Completion Date
    July 30, 2024 (Anticipated)
    Study Completion Date
    December 30, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Sixth Affiliated Hospital, Sun Yat-sen University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    In moderate to severe cavity adhesions, the endometrial basal layer is more severely damaged and the regenerative capacity of the endometrium and glands is low. Even though hysteroscopic electrosurgery can roughly restore the cavity morphology, the postoperative recurrence rate is as high as 40%. Abnormal uterine cavity morphology and poor endometrial repair often lead to repeated cancellation of embryo transfer cycles in assisted reproduction treatment, and reduced clinical pregnancy rate, causing mental stress and financial burden to patients, which is one of the current problems in clinically assisted reproduction treatment. Nintedanib is a triple vascular kinase inhibitor that acts primarily on platelet-derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR) and has been approved by the FDA for the clinical treatment of idiopathic pulmonary fibrosis and systemic sclerosis. The investigator's preliminary animal study found that endometrial fibrosis was significantly reduced in mice with gastric feeding of nintedanib in uterine adhesion molds. This study aimed to clarify further the role of nintedanib in inhibiting endometrial fibrosis and its clinical application value.
    Detailed Description
    The experiment will be divided into two groups based on the dose administered. After hysteroscopic surgery, one group will be given Nedanib 100mg bid orally for 15 days and the other group will be given Nedanib 150mg bid orally for 15 days. Hysteroscopic AFS scores and endometrial tissues before and after treatment will be collected for molecular biology experiments.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Uterine Adhesions
    Keywords
    uterine adhesions, endometrail fibrisis

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    90 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Nintedanib 100mg
    Arm Type
    Experimental
    Arm Description
    Traditional hormone replacement (HRT) cycle medication (Tegretol 2mg bid for 20 days, followed by Darvon 10mg bid for the last 10 days) + Nintedanib 100mg bid *15 days orally.
    Arm Title
    Nintedanib 150mg
    Arm Type
    Experimental
    Arm Description
    Traditional hormone replacement (HRT) cycle medication (Tegretol 2mg bid for 20 days, followed by Darvon 10mg bid for the last 10 days) + Nintedanib 150mg bid *15 days orally.
    Intervention Type
    Drug
    Intervention Name(s)
    Nintedanib 100 MG [Ofev]
    Other Intervention Name(s)
    Nintedanib 100 MG Oral Capsule
    Intervention Description
    Nintedanib 100mg bid *15 days orally after hysteroscopic surgery
    Intervention Type
    Drug
    Intervention Name(s)
    Nintedanib 150 MG [Ofev]
    Other Intervention Name(s)
    Nintedanib 150 MG Oral Capsule
    Intervention Description
    Nintedanib 150mg bid *15 days orally after hysteroscopic surgery
    Primary Outcome Measure Information:
    Title
    American Fertility Association(AFS) score (mild:1-4,moderate:5-8,severe:9-12)
    Description
    American Fertility Association(AFS) scoring performed hysteroscopically
    Time Frame
    3 months
    Secondary Outcome Measure Information:
    Title
    Endometrial thickness
    Description
    Endometrial thickness measured by ultrasonography
    Time Frame
    3 months

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    20 Years
    Maximum Age & Unit of Time
    38 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 1)Clinical diagnosis of uterine adhesions; 2)Body mass index between 18-27 kg/m2; 3)Have a regular menstrual cycle of 27-35 days for at least six months; 4)Hysteroscopic diagnosis of moderate to severe uterine adhesions (AFS score >5), treated with electrodesiccation; 5)No contraindications to oral estrogen and progestin such as a history of thrombosis/breast tumor/history of abnormal liver function/migraine; 6)≥ 2 oocytes or blastocysts have been frozen. Exclusion Criteria: 1)Patients with combined ovarian cysts ≥ 20 mm in diameter, submucosal uterine fibroids or intermuscular fibroids > 30 mm in diameter, pituitary tumors, and malignant tumors of various tissues and organs; 2)Patients with clinically significant abnormalities of the uterus (endometrial polyps, uterine malformations, endometriosis) and adnexa (hydrosalpinx); 3)Repeated implantation failures, such as three consecutive transfers with ≥6 failed high-quality embryos; 4)Known malformations of the reproductive organs that are unsuitable for pregnancy; 5)Abnormal cervical cytology (TCT) findings within 1 year before the screening; 6)Severe liver or kidney impairment, heart disease, or hypertension; 7)Known previous or current history of thrombophlebitis or thromboembolic disease; 8)Any known clinically significant systemic disease (e.g., diabetes mellitus, tuberculosis, etc; 9)Known history of recurrent miscarriage; 10)Chromosomal karyotype abnormalities in either spouse; 11)Genetic disorders that make either spouse unsuitable for childbirth as specified in the Maternal and Child Health Law;12)exposure of either spouse to teratogenic amounts of radiation, toxins, and drugs; 13)Participation in another drug or medical device clinical trial within 3 months before enrollment;14)Any medical condition/combined surgery/ medication/other clinically significant abnormal laboratory tests that, in the judgment of the investigator, may affect the outcome of the trial; 15)Known refusal or inability to comply with protocol requirements for any reason (including planned clinical visits and examinations).

    12. IPD Sharing Statement

    Learn more about this trial

    Prospective Clinical Study of Nintedanib to Inhibit Endometrial Fibrosis to Prevent Recurrence of Uterine Adhesions

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