Efficacy and Dose Ranging Study of Seroguard

Study Overview
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Brief Summary
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This trial was a multi-center, double-blind, randomized, parallel group, placebo-controlled, phase II study in adult hospitalized female patients with the confirmed diagnosis of pelvic adhesive disease in Study centres in Russia.

Detailed Description
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In order to evaluate efficacy and safety of Seroguard, solution for IP administration, a study design meeting the set objectives was selected: prospective, multi-center, double-blind, randomized, parallel group, placebo-controlled study. Given the fact that comparison with placebo is considered the best way to prove efficacy and safety of a drug and that currently there are no drugs with a similar mechanism of action at the pharmaceutical product market, a placebo-controlled, parallel group study design was selected. A randomized, parallel group study design was chosen in order to ensure minimization of a selection bias. Subjects were randomized into four groups (two groups of the test drug and two placebo groups corresponding to the two doses) to enable a comparison of Seroguard administration at two doses. A double-blind study design was selected in order to ensure minimization of an outcome evaluation bias.

Official Title
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Phase II Multi-center Randomized Double-blind Placebo-controlled Efficacy and Dose Ranging Trial of the Drug Product Seroguard, Solution (JSC Pharmasyntez, Russia) Used for the Prevention of Pelvic Adhesions

Conditions
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Adhesion

Intervention / Treatment
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* Drug: Seroguard
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients aged from 18 to 45 years with the confirmed diagnosis of pelvic adhesions having indications for surgery (laparoscopic adhesiolysis). Voluntarily and personally signed and dated Form of Informed Consent. Female patients with pelvic adhesions confirmed by gynecological and ultrasound examination. Exclusion Criteria: Female patients having contraindications to surgical treatment (including acute or exacerbated chronical adnexal inflammation); Body mass index of 30.0 kg/m2 and more; Known hypersensitivity to the test drug components (Seroguard); Pregnancy, breastfeeding or planning a pregnancy during the clinical trial; Refusal to use effective contraception methods throughout the study; Positive HIV, RW, HBV or HCV test result; Alcohol abuse, drug addiction, and toxicomania (except smoking); American Society of Anesthesiologists physical status category III and more (ASA); Purulent process in the abdominal cavity; Disseminated endometriosis; WBC count more than 10*109/L at the complete blood count; Need of using any drugs during the surgery other than 0.02% chlorhexidine aqueous solution throughout the surgery, as well as the test drug or the placebo (0.9% sodium chloride) administered intraperitoneally in the end of surgery. Concomitant diseases that may require conversion of the surgical intervention by other indications; Type I or II diabetes mellitus; Deep vein thrombosis and/or PATE at the screening or in the medical history; Renal impairment (glomerular filtration rate less than 60 mL/min/1.73 m2 assessed by the CKD-EPI equation); Liver disorders defined as more than 2-fold rise of the upper limit of normal of one of the following enzymes: ALT, AST, GGTP, AP, or more than 2-fold total bilirubin increase; Myocardial infarction within 6 months before screening; Any concomitant diseases accompanied by heart failure; Clinically significant ECG changes (as to the investigator's opinion); Any concomitant diseases accompanied by respiratory failure; Any oncological disease within 3 years before enrollment into the study; Systemic inflammatory diseases; Diseases associated with chronic hemorrhages; Blood diseases (anemias of any origin, hemoglobinopathies, inherited and acquired coagulopathies, hemostasis disorders, thrombocytopenias, and thrombocytopathias, any hemoblastoses); Any other disease that, in the investigator's opinion, may affect study results or present an additional threat to well-being of a patient after administration of the study drug; Use of anticoagulants, antiaggregants (except for acetylsalicylic acid at the dose of less than 325 mg/day) at the moment of inclusion into the study or planning to do so during the study; Use of drugs with pronounced hemato-, hepato-, or nephrotoxic action, drugs of biological origin; Need to administer cytostatics, systemic glucocorticosteroids, and other immunosuppressive agents during the patient's participation in the study. Participation in any other clinical trial within 30 days before screening; Contraindications to MRI (presence of implants or implanted electronic devices); Impossibility or inability to comply with the requirements of the protocol, including for physical, psychic or social reasons, in the investigator's opinion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo, 1.5 mL/kg<br>each subject received the placebo at the dose of 1.5 mL/kg of body weight; | Drug: Placebo<br>* Saline<br>|
| Placebo Comparator: Placebo, 2.4 mL/kg<br>each subject received the placebo at the dose of 2.4 mL/kg of body weight; | Drug: Placebo<br>* Saline<br>|
| Experimental: Seroguard, 1.5 mL/kg<br>each subject received the test drug at the dose of 1.5 mL/kg of body weight; | Drug: Seroguard<br>* Seroguard 0.41 g/L solution<br>|
| Experimental: Seroguard, 2.4 mL/kg<br>each subject received the test drug at the dose of 2.4 mL/kg of body weight. | Drug: Seroguard<br>* Seroguard 0.41 g/L solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Reduction of Adhesions Number by 3 or More | The number of adhesions according to the first MRI data was compared to the number according to the data of second MRI | 30±4 days after surgical intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Thickness of Pelvic Adhesions | The change from baseline was defined. It was evaluated by comparing baseline MRI data and repeated MRI data. Results were estimated according to scale from 0 to 3 where 0 - no adhesions, 1 - thin (filmy or filiform), 2 - marked, 3 - marked with an impaired passage through organs involved. | 30±4 days after surgery | 
| Number of Participants With Detection of Pelvic Organs Limited Mobility | The frequency was estimated based on transvaginal ultrasound results | 30±4 days after surgery | 
| Number of Participants With Detection of Hyperechoic Linear Lesions Post Surgery | The frequency was estimated based on transvaginal ultrasound results | 30±4 days after surgery | 
| Change in Number of Participants in Detecting Pelvic Organs Limited Mobility | Absolute change of count of participants was measured with detecting pelvic organs limited mobility from the baseline | 30±4 days after surgery | 
| Change Number of Participants in Detecting Hyperechoic Linear Lesions | Frequency of detecting after repeated transvaginal ultrasound results was compared to baseline indications (4 or more) | 30±4 days after surgery | 
| Number of Participants With Detection of no Ultrasound Signs of Pelvic Adhesive Disease Post Surgery | No limited mobility of pelvic organs and no hyperechoic linear lesions should be shown | 30±4 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adhesion, Efficacy