Remaxol® in Patients With Drug-induced Liver Injuries During Cancer Chemotherapy

Polysan

Status: Completed

Conditions: Drug Induced Liver Injury; Cancer

Treatments: Drug: Remaxol

Study type: Observational

Funder types: Industry

Identifiers

NCT05789797

Remaxol\2022\03

Details and patient eligibility

About

Cancer has moved from the tenth place to the second one over the last 100 years, being inferior to only cardiovascular diseases in morbidity and mortality.

40 % of hepatitis cases in patients older than 40 years and 25 % of cases of fulminant hepatic failure (FHF) are caused by drug hepatic toxicity. Cases of acute drug-induced hepatitis (ADIH) make 15-20 % of patients with fulminant hepatitis in Western Europe.

Enrollment: 368 patients

Sex: All

Ages: 40 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• The study can include all patients who are scheduled, at a physician's discretion, to receive the therapy with the drug Remaxol®, solution for infusions, or Ademethionine, lyophilizate for solution for intravenous and intramuscular injection, according to the approved instruction for the medical use of the drug and established clinical practice of a healthcare facility, and who meet all the following criteria:

  1. Males and females aged from 40 to 70 years inclusive.

  2. Verified diagnosis of neoplasm (morphologically proven).

  3. Receiving the course polychemotherapy (PCT).

  4. PCT regimens with pronounced hepatotoxic effects, which use drugs from the following pharmacologic classes:

     1. Competitive antagonists (5-Fluorouracil, Methotrexate etc.);
     2. Alkylating agents (Cyclophosphamide, Oxaliplatin etc.);
     3. Antitumor antibiotics (Doxorubicin, Bleomycin etc.);
     4. Drugs influencing tubulin (Trabectedin, Paclitaxel etc.);
     5. Topoisomerase inhibitors (Irinotecan, Etoposide etc.).
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  1. Contraindications for the continuation of PCT at the time of a visit to a physician for its continuation, because of developed hepatotoxicity.
  2. Stage of the treatment: supporting, hepatoprotective and detoxication therapy to correct hepatotoxicity developed during PCT, to remove it and continue the chemotherapeutic treatment.
  3. A patient is scheduled to receive one of the following infusion therapies with the following regimen, as part of the routine clinical practice:
  4. It is planned to administer the drug Remaxol®, solution for infusions, by intravenous drop infusion in the dose of 400 ml/day, on everyday basis for 12 days.
  5. It is planned to administer the drug Ademethionine, lyophilisate for solution for intravenous and intramuscular injection, by intravenous drop infusion in the dose of 800 mg/day, on everyday basis for 14 days. ECOG performance status score: 1-2 inclusive (Karnofsky score: 50-80 %).
  6. Hepatotoxicity grade according to the classification of the US National Cancer Institute (NCCN, CTC) - 2 and 3.
  7. Scores by selected parameters of CTCAE (National Cancer Institute Common Toxicity Criteria for Adverse Events) scale - I and II.
  8. Patient's written consent for participation in the study according to the current legislation.

Exclusion criteria

1. Pregnancy, breast-feeding.
2. Mental disorders requiring psychiatric observation.
3. Chronic alcohol abuse and/or substance abuse.
4. HIV-infection, syphilis, virus hepatitis, autoimmune hepatitis, storage diseases, tuberculosis.
5. Administration of monoclonal antibodies, (multi)kinase inhibitors during the PCT session immediately preceding this study.
6. Administration of methionine-, Ademetionine-, malate- and/or succinate-containing medicines during the last month.
7. Prescription of other malate-, succinate, or methionine-containing medicines (mexidol, cytoflavin, etc.).
8. Decompensation of any severe/clinically apparent somatic diseases of the kidneys, liver, cardiovascular system, respiratory system, endocrine system, etc., as decided by the investigating physician.
9. Contraindications mentioned in the approved instructions for use of medicines applied in the study (idiosyncrasy to the product components).
10. Disease or use of medicines, which, in the doctor's opinion, can influence safety, tolerability and efficiency of the study medicines.

Trial design

368 participants in 2 patient groups

The control group

Description:

Ademethionine, lyophilisate for solution for intravenous and intramuscular injection, by intravenous drop infusion in the dose of 800 mg/day, on everyday basis for 14 days

The test group

Description:

Remaxol®, solution for infusions, by intravenous drop infusion in the dose of 400 ml/day, on everyday basis for 12 days

Treatment:

Drug: Remaxol