A Study to Evaluate Dimolegin in Prevention of Thromboembolic Complications During Knee Replacement

NCT05189002 | Unknown Phase 2 DMC

• 1 other identifier: AM217-02
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 15

Brief Summary

This study is a multicenter, double-blind, randomized, prospective phase 2 dose ranging study to evaluate the safety and efficacy of Dimolegin - DD217 in prevention of venous thromboembolic complications in patients underwent knee replacement. The study model is at each stage in parallel groups. Dimolegin - DD217 efficacy and safety in prevention of venous thromboembolic complications during knee replacement in groups of 80 patients will be investigated. Patients who meet all inclusion criteria and none of the exclusion criteria will be randomized into three therapy groups: two therapy groups of the test drug Dimolegin - DD217 (40 mg (group 1a) and 60 mg (group 1b)) and one reference group (Fragmin). Bilateral phlebography (preferably) or ultrasound duplex scanning (USDS) will be performed on the Day of the V13 visit. It is planned to randomize 240 patients (160 patients in two different groups of Dimolegin - DD217 therapy and 80 patients in the reference group of Fragmin (INN: dalteparin). The number of patients included in the study and randomized to receive Dimolegin - DD217, at the first stage, can be increased in the case of starting recruitment to additional group 1b. The maximum number of patients who can be included in the study at the first stage is 320. In total, no more than 480 patients can take part in the screening. Pharmacokinetic (PK) and pharmacodynamic (PD) parameters will be determined in patients who voluntarily give their consent to participate in the pharmacokinetic study (PKS) and pharmacodynamic study (PDS) and sign a Patient Information Leaflet with an informed consent form for participation in the PKS and PDS. PK parameters are planned to be determined in 18-20 patients (50 % of each sex) in each patient group. Participation in the voluntary part of PK study will be offered to all patients. The analysis of the composite endpoint frequency will be carried out using a generalized linear model for binary response. A formal conclusion about superiority will be made if the lower limit of the specified confidence intervals exceeds the value of 0.0. A formal conclusion on non-inferiority will be made if the lower limit of the specified confidence intervals exceeds the value of -0.05 (-5.0 %).

Conditions

Venous Thromboembolism

Keywords

Dimolegin; Dioxaban; DD217; factor Xa Inhibitor; anticoagulant; therapeutic anticoagulation; thromboprophylaxis; thrombosis; venous thromboembolism; knee replacement; anticoagulation

Outcome Measures

Primary Outcomes (1)

• The total venosus thromboembolism (VTE) index

  The frequency of composite endpoint, which includes: * Asymptomatic deep vein thrombosis (DVT) detected by bilateral phlebography (preferably) or USDS at Visit V13 (Day D14±1); * Objectively confirmed by phlebography, USDS, computed tomography or other method symptomatic or asymptomatic DVT before Visit V13 (Day D14±1) inclusive; * Non-fatal PE before Visit V13 (Day D14±1) inclusive; * Fatal PE before Visit V13 (Day D14±1) inclusive; * Unexplained death, in which pulmonary embolism (PE) cannot be excluded before the Visit V13 (Day D14 ± 1) inclusive.

  14 Days

Secondary Outcomes (1)

• The total venosus thromboembolism (VTE) index (W6)

  6 Weeks

Other Outcomes (2)

• The frequency of cumulative major and clinically significant minor bleeding on Visits V1- V13

  14 Days

• The frequency of cumulative major and clinically significant minor bleeding before Visit V15

  6 Weeks

Study Arms (3)

Group 1a

EXPERIMENTAL

Patients from groups 1a took the study product once a day in doses 40 mg per os and saline solution subcutaneously. Dose was blinded for a patient and investigator (double-blind method) using six tablets for each administration, some of them contained Dimolegin - DD217, and others were masked as Placebo of the study product.

Drug: Dimolegin 40 mg

Group 1b

EXPERIMENTAL

Patients from groups 1b took the study product once a day in doses 60 mg per os and saline solution subcutaneously. Dose was blinded for a patient and investigator (double-blind method) using six tablets for each administration, some of them contained Dimolegin - DD217, and others were masked as Placebo of the study product.

Drug: Dimolegin 60 mg

Group 2

ACTIVE COMPARATOR

Patients from the control group (group 2) were received Fragmin in accordance with the instruction for medical use (5000 IU s/c once a day with 24-hour interval) and six Placebo tablets masked as study product Dimolegin - DD217 once a day.

Drug: Fragmin

Interventions

Dimolegin 40 mg DRUG

Dimolegin - DD217 - 40 mg

Also known as: DD217

Group 1a

Dimolegin 60 mg DRUG

Dimolegin - DD217 - 60 mg

Also known as: DD217

Group 1b

Fragmin DRUG

Fragmin 5000 IU in 0.2 ML Prefilled Syringe

Also known as: Dalteparin sodium

Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18 years and older who need elective primary total knee replacement (cement or cementless arthroplasty)
• Signed informed consent
• Ability to comply with all protocol requirements
• Patients' consent to use adequate methods of contraception throughout the study

You may not qualify if:

• Surgery for an acute fracture 4 weeks before screening; septic inflammation of the joint, revision of the prosthesis or the absence of one leg
• Venous thrombosis of any localization or a confirmed PE episode at the present time or in the medical history
• Heparin-induced thrombocytopenia or other thrombocytopathies currently or in the history, hemorrhagic diathesis
• Obvious coagulopathy ongoing or in the history of the patient or a blood relative
• Congenital thrombophilia according to the medical history (deficiency of antithrombin III, protein C, protein S, Leiden mutation of coagulation factor V, increased level of coagulation factor VIII, mutation of prothrombin G20210A)
• Active bleeding (intracranial, intraocular, nasal, digestive or other localization) at present or within 6 months prior to screening, high risk of bleeding
• Collection of at least one volume unit of donated blood (\> 500 mL) or blood transfusion during the previous 12 weeks
• Surgery on the brain or spinal cord, spine, ophthalmic or major surgery or injury in the last 90 days
• Gastrointestinal tract disorders that can disrupt the absorption of the study drug (Crohn's disease, ulcerative colitis, irritable bowel syndrome)
• Acute gastric or duodenal ulcer, erosive gastritis with increased risk of bleeding
• Significant cardiovascular diseases ongoing or within 6 months prior to screening, including: chronic heart failure of class III or IV (according to the classification of the New York Heart Association), myocardial infarction, unstable angina, surgery on the heart and coronary vessels (including percutaneous coronary intervention with or without coronary artery stenting), significant diseases of the heart valves, hemodynamically significant cardiac arrhythmias, transient ischemic attack, ischemic or hemorrhagic stroke, uncontrolled hypertension
• Active liver disease (viral hepatitis B or C, cirrhosis of the liver) and biliary tract disease, with the exception of non-alcoholic steatohepatitis with normal levels of hepatic transaminases (ALT and AST)
• Nephrotic syndrome, significant kidney diseases with the events of nephrotic syndrome (decreased filtration renal function with decreased estimated glomerular filtration rate (eGFR) \< 60 according to the MDRD formula (MDRD)
• Malignant neoplasms during the last 5 years (with the exception of basal cell carcinoma for which radical treatment was carried out).
• Positive test for HIV, syphilis, hepatitis B or C markers (HBsAg and Anti-HCV)

Sponsors & Collaborators

• PharmaDiall Ltd.: lead

Study Sites (15)

GAUZ Bryansk City Hospital No. 1

Bryansk, 241035, Russia

Location

Federal State Budgetary Institution National Medical Research Center of Traumatology and Orthopedics named after Academician G.A. Ilizarov the Ministry of Health of the Russian Federation

Kurgan, 640014, Russia

Location

A budgetary medical institution Kursk Regional Clinical Hospital of the Health Committee of the Kursk Region

Kursk, 305007, Russia

Location

GBUZ of the city of Moscow City Clinical Hospital No. 1 named after NI Pirogova of the Moscow City Health Department

Moscow, 119049, Russia

Location

Federal State Budgetary Scientific Institution Russian Scientific Center for Surgery named after Academician B.V. Petrovsky

Moscow, 119991, Russia

Location

GBUZ Moscow GKB im. S.P. Botkin of the Department of Health of the city of Moscow

Moscow, 125284, Russia

Location

GBUZ of the Moscow region MONIKI them. M.F. Vladimirsky

Moscow, 129110, Russia

Location

FBUZ Privolzhsky District Medical Center FMBA

Nizhny Novgorod, 603001, Russia

Location

FSBEI HE Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation

Nizhny Novgorod, 603005, Russia

Location

GBUZ Penza Regional Clinical Hospital named after N.N. Burdenko

Penza, 440026, Russia

Location

Federal State Budgetary Educational Institution of Higher Education Ryazan State Medical University named after Academician I.P. Pavlova of the Ministry of Health of the Russian Federation

Ryazan, 390026, Russia

Location

St. Petersburg GBUZ City Hospital of the Holy Martyr Elizabeth

Saint Petersburg, 197706, Russia

Location

FGBUZ Samara Regional Clinical Hospital named after V. D. Seredavin

Samara, 443095, Russia

Location

GBUZ of the Republic of Mordovia Mordovian Republican Central Clinical Hospital

Saransk, 430013, Russia

Location

FSBI Federal Center for Traumatology, Orthopedics and Endoprosthetics of the Ministry of Health of the Russian Federation

Smolensk, 214031, Russia

Location

Related Publications (2)

• Tovbin DG, Tarasov DN, Malakhov DV, Tserkovnikova NA, Aybush AV, Drozd NN. The Development of New Low-Molecular-Weight Factor Xa Inhibitors that are Potential Anticoagulants. Curr Drug Discov Technol. 2022;19(1):e010921191770. doi: 10.2174/1568009621666210224104940.

  PMID: 33655836 BACKGROUND

• Tarasov DN, Tovbin DG, Malakhov DV, Aybush AV, Tserkovnikova NA, Savelyeva MI, Sychev DA, Drozd NN, Savchenko AY. The Development of New Factor Xa Inhibitors Based on Amide Synthesis. Curr Drug Discov Technol. 2018;15(4):335-350. doi: 10.2174/1570163815666180215114732.

  PMID: 29468977 BACKGROUND

MeSH Terms

Conditions

Venous Thromboembolism; Thrombosis

Interventions

(+-)-(1'R*,2'S*,6'R*)-(2-hydroxy-4,6-dimethoxyphenyl)(3'-methyl-2'-(3''-methylbut-2''-enyl)-6-phenylcyclohex-3'-enyl)methanone; Dalteparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Dmitry A Napalkov, Professor

  Department of Faculty Therapy No. 1 of the Sechenov University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Dose Dimolegin - DD217 in each group was blinded for a patient and investigator (double-blind method) using six tablets for each administration, some of them contained Dimolegin - DD217, and others were masked as Placebo of the study product
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, double blind, randomized, prospective

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: January 12, 2022
• Study Start: May 31, 2019
• Primary Completion: August 31, 2021
• Study Completion: December 31, 2022
• Last Updated: May 2, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (15)