Adhesion
Conditions
Keywords
Adhesion, Efficacy
Brief summary
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
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.
Interventions
DRUGSeroguard
Seroguard 0.41 g/L solution
DRUGPlacebo
Saline
Sponsors
Cromos Pharma LLC
Pharmasyntez
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
The present study was conducted as a double blind trial. Neither a medical investigator, nor patients had access to the treatment assignment code in order to ensure the maximum objective evaluation of the primary endpoint. Blinding was performed in such a way that disclosing a randomization code of a certain subject excluded a disclosure of the code in general (i.e. the randomization code had no indication to the treatment group). However, there were no cases of the randomization code disclosure in the study
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Female patients aged from 18 to 45 years with the confirmed diagnosis of pelvic adhesions having indications for surgery (laparoscopic adhesiolysis). 2. Voluntarily and personally signed and dated Form of Informed Consent. 3. Female patients with pelvic adhesions confirmed by gynecological and ultrasound examination.
Exclusion criteria
1. Female patients having contraindications to surgical treatment (including acute or exacerbated chronical adnexal inflammation); 2. Body mass index of 30.0 kg/m2 and more; 3. Known hypersensitivity to the test drug components (Seroguard); 4. Pregnancy, breastfeeding or planning a pregnancy during the clinical trial; 5. Refusal to use effective contraception methods throughout the study; 6. Positive HIV, RW, HBV or HCV test result; 7. Alcohol abuse, drug addiction, and toxicomania (except smoking); 8. American Society of Anesthesiologists physical status category III and more (ASA); 9. Purulent process in the abdominal cavity; 10. Disseminated endometriosis; 11. WBC count more than 10\*109/L at the complete blood count; 12. 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. 13. Concomitant diseases that may require conversion of the surgical intervention by other indications; 14. Type I or II diabetes mellitus; 15. Deep vein thrombosis and/or PATE at the screening or in the medical history; 16. Renal impairment (glomerular filtration rate less than 60 mL/min/1.73 m2 assessed by the CKD-EPI equation); 17. 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; 18. Myocardial infarction within 6 months before screening; 19. Any concomitant diseases accompanied by heart failure; 20. Clinically significant ECG changes (as to the investigator's opinion); 21. Any concomitant diseases accompanied by respiratory failure; 22. Any oncological disease within 3 years before enrollment into the study; 23. Systemic inflammatory diseases; 24. Diseases associated with chronic hemorrhages; 25. Blood diseases (anemias of any origin, hemoglobinopathies, inherited and acquired coagulopathies, hemostasis disorders, thrombocytopenias, and thrombocytopathias, any hemoblastoses); 26. 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; 27. 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; 28. Use of drugs with pronounced hemato-, hepato-, or nephrotoxic action, drugs of biological origin; 29. Need to administer cytostatics, systemic glucocorticosteroids, and other immunosuppressive agents during the patient's participation in the study. 30. Participation in any other clinical trial within 30 days before screening; 31. Contraindications to MRI (presence of implants or implanted electronic devices); 32. Impossibility or inability to comply with the requirements of the protocol, including for physical, psychic or social reasons, in the investigator's opinion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reduction of Adhesions Number by 3 or More | 30±4 days after surgical intervention | The number of adhesions according to the first MRI data was compared to the number according to the data of second MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Detection of Pelvic Organs Limited Mobility | 30±4 days after surgery | The frequency was estimated based on transvaginal ultrasound results |
| Number of Participants With Detection of Hyperechoic Linear Lesions Post Surgery | 30±4 days after surgery | The frequency was estimated based on transvaginal ultrasound results |
| Change in Thickness of Pelvic Adhesions | 30±4 days after surgery | 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. |
| Change Number of Participants in Detecting Hyperechoic Linear Lesions | 30±4 days after surgery | Frequency of detecting after repeated transvaginal ultrasound results was compared to baseline indications (4 or more) |
| Number of Participants With Detection of no Ultrasound Signs of Pelvic Adhesive Disease Post Surgery | 30±4 days after surgery | No limited mobility of pelvic organs and no hyperechoic linear lesions should be shown |
| Change in Number of Participants in Detecting Pelvic Organs Limited Mobility | 30±4 days after surgery | Absolute change of count of participants was measured with detecting pelvic organs limited mobility from the baseline |
Countries
Russia
Participant flow
Pre-assignment details
114 is the number of enrolled and screened participants according to the protocol, but during the screening process some people were withdrawn from the study before randomization because some of them did not meet the inclusion criteria and some withdrew the informed consent form themselves. So, the number of randomized participants is 104.
Participants by arm
| Arm | Count |
|---|---|
| Placebo, 1.5 mL/kg each subject received the placebo at the dose of 1.5 mL/kg of body weight;
Placebo: Saline | 26 |
| Placebo, 2.4 mL/kg each subject received the placebo at the dose of 2.4 mL/kg of body weight;
Placebo: Saline | 26 |
| Seroguard, 1.5 mL/kg each subject received the test drug at the dose of 1.5 mL/kg of body weight;
Seroguard: Seroguard 0.41 g/L solution | 26 |
| Seroguard, 2.4 mL/kg each subject received the test drug at the dose of 2.4 mL/kg of body weight.
Seroguard: Seroguard 0.41 g/L solution | 26 |
| Total | 104 |
Baseline characteristics
| Characteristic | Placebo, 1.5 mL/kg | Placebo, 2.4 mL/kg | Seroguard, 1.5 mL/kg | Seroguard, 2.4 mL/kg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 26 Participants | 26 Participants | 26 Participants | 104 Participants |
| Age, Continuous | 31.0 years STANDARD_DEVIATION 6.2 | 31.6 years STANDARD_DEVIATION 5.3 | 31.6 years STANDARD_DEVIATION 5.4 | 31.6 years STANDARD_DEVIATION 5.4 | 31.5 years STANDARD_DEVIATION 5.6 |
| Race/Ethnicity, Customized Caucasian race | 26 Participants | 26 Participants | 26 Participants | 26 Participants | 104 Participants |
| Region of Enrollment Russia | 26 participants | 26 participants | 26 participants | 26 participants | 26 participants |
| Sex: Female, Male Female | 26 Participants | 26 Participants | 26 Participants | 26 Participants | 104 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 26 |
| other Total, other adverse events | 3 / 25 | 2 / 25 | 1 / 25 | 0 / 26 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 | 0 / 25 | 0 / 26 |
Outcome results
Primary
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
Time frame: 30±4 days after surgical intervention
Population: 7 patients had no results of repeated Pelvic MRI examination that is why the number of Participants is different
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo, 1.5 mL/kg | Number of Participants With Reduction of Adhesions Number by 3 or More | 1 Participants |
| Placebo, 2.4 mL/kg | Number of Participants With Reduction of Adhesions Number by 3 or More | 1 Participants |
| Seroguard, 1.5 mL/kg | Number of Participants With Reduction of Adhesions Number by 3 or More | 10 Participants |
| Seroguard, 2.4 mL/kg | Number of Participants With Reduction of Adhesions Number by 3 or More | 10 Participants |
Secondary
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
Time frame: 30±4 days after surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, 1.5 mL/kg | Change in Number of Participants in Detecting Pelvic Organs Limited Mobility | -17 participants |
| Placebo, 2.4 mL/kg | Change in Number of Participants in Detecting Pelvic Organs Limited Mobility | -17 participants |
| Seroguard, 1.5 mL/kg | Change in Number of Participants in Detecting Pelvic Organs Limited Mobility | -21 participants |
| Seroguard, 2.4 mL/kg | Change in Number of Participants in Detecting Pelvic Organs Limited Mobility | -21 participants |
Secondary
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.
Time frame: 30±4 days after surgery
Population: 7 patients had no results of repeated Pelvic MRI examination that is why the number of Participants is different
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo, 1.5 mL/kg | Change in Thickness of Pelvic Adhesions | 0 score on a scale |
| Placebo, 2.4 mL/kg | Change in Thickness of Pelvic Adhesions | 0 score on a scale |
| Seroguard, 1.5 mL/kg | Change in Thickness of Pelvic Adhesions | 0 score on a scale |
| Seroguard, 2.4 mL/kg | Change in Thickness of Pelvic Adhesions | 0 score on a scale |
Secondary
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)
Time frame: 30±4 days after surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, 1.5 mL/kg | Change Number of Participants in Detecting Hyperechoic Linear Lesions | -17 participants |
| Placebo, 2.4 mL/kg | Change Number of Participants in Detecting Hyperechoic Linear Lesions | -16 participants |
| Seroguard, 1.5 mL/kg | Change Number of Participants in Detecting Hyperechoic Linear Lesions | -19 participants |
| Seroguard, 2.4 mL/kg | Change Number of Participants in Detecting Hyperechoic Linear Lesions | -18 participants |
Secondary
Number of Participants With Detection of Hyperechoic Linear Lesions Post Surgery
The frequency was estimated based on transvaginal ultrasound results
Time frame: 30±4 days after surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, 1.5 mL/kg | Number of Participants With Detection of Hyperechoic Linear Lesions Post Surgery | 3 participants |
| Placebo, 2.4 mL/kg | Number of Participants With Detection of Hyperechoic Linear Lesions Post Surgery | 2 participants |
| Seroguard, 1.5 mL/kg | Number of Participants With Detection of Hyperechoic Linear Lesions Post Surgery | 1 participants |
| Seroguard, 2.4 mL/kg | Number of Participants With Detection of Hyperechoic Linear Lesions Post Surgery | 3 participants |
Secondary
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
Time frame: 30±4 days after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo, 1.5 mL/kg | Number of Participants With Detection of no Ultrasound Signs of Pelvic Adhesive Disease Post Surgery | 19 Participants |
| Placebo, 2.4 mL/kg | Number of Participants With Detection of no Ultrasound Signs of Pelvic Adhesive Disease Post Surgery | 19 Participants |
| Seroguard, 1.5 mL/kg | Number of Participants With Detection of no Ultrasound Signs of Pelvic Adhesive Disease Post Surgery | 23 Participants |
| Seroguard, 2.4 mL/kg | Number of Participants With Detection of no Ultrasound Signs of Pelvic Adhesive Disease Post Surgery | 20 Participants |
Secondary
Number of Participants With Detection of Pelvic Organs Limited Mobility
The frequency was estimated based on transvaginal ultrasound results
Time frame: 30±4 days after surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, 1.5 mL/kg | Number of Participants With Detection of Pelvic Organs Limited Mobility | 4 participants |
| Placebo, 2.4 mL/kg | Number of Participants With Detection of Pelvic Organs Limited Mobility | 4 participants |
| Seroguard, 1.5 mL/kg | Number of Participants With Detection of Pelvic Organs Limited Mobility | 0 participants |
| Seroguard, 2.4 mL/kg | Number of Participants With Detection of Pelvic Organs Limited Mobility | 2 participants |