Remaxol® in Malignant Mechanical Jaundice

A Multicenter, Double-blind, Placebo-controlled, Randomized Trial of the Efficacy and Safety of Remaxol®, a Solution for Infusions Produced by STPF POLYSAN (Russia), in Patients With Malignant Mechanical Jaundice

The trial intends to study the safety and efficacy of Remaxol® (succinate + methionine + inosine + nicotinamide; POLYSAN Ltd., Russia),solution for infusion for the reduction of hyperbilirubinemia in patients with obstructive jaundice caused by tumor (malignancy).

Study Overview

Status

Completed

Conditions

Detailed Description

The study will recruit in-hospital surgical patients with obstructive jaundice caused by malignancies of pancreatic and hepatobiliary zone.

The study consists of the following periods:

  • Screening - preliminary examination of patients (duration up to 3 days).
  • Period of therapy (including surgery and postoperative period) - treatment with the investigational product Remaxol®, solution for infusions, (NTFF POLYSAN Ltd., Russia) or placebo, as part of standard infusion therapy during the postoperative period of patients with mechanical jaundice of malignant origin (duration 10 days).
  • The period of follow-up (duration - 3 weeks after the end of treatment).

After the screening, patients who meet the inclusion criteria and do not have exclusion criteria will be randomly assigned to three groups (1:1:1):

  • Group I: treatment with Remaxol® 400 ml IV, and placebo (Ringer solution) 400 ml IV, once a day for 10 days, along with standard infusion therapy.
  • Group II: treatment Remaxol® 800 ml IV, once a day for 10 days, along with standard infusion therapy.
  • Group III: patients will receive placebo ((Ringer solution) 800 ml IV, once a day for 10 days, along with standard infusion therapy.

Assessment will include physical examination data, vital signs, blood tests (CBC, biochemistry - protein, albumin, AST, ALT, APG, GGTP, LDH, total bilirubin, direct bilirubin, amylase, glucose, electrolytes, creatinine, urea, uric acid, C -reactive protein, lipid profile; coagulogram; urine samples), ECOG assessment, repeated abdominal ultrasound, neurophysiological test for the evaluation of encephalopathy, record of bile volume by drainage (if applicable).

All patients will be followed up for 31 days.

Study Type

Interventional

Enrollment (Actual)

240

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bryansk, Russian Federation
        • GBUZ 'Bryansk City Hospital #1'
      • Kemerovo, Russian Federation
        • Regional Clinical Hospital of Emergency Care n.a.M.A.Podgorbunsky
      • Krasnoyarsk, Russian Federation
        • KBUZ 'Regional Clinical Hospital'
      • Kursk, Russian Federation
        • OBUZ 'Kursy Regional Clinical Oncology Dispensary' of Kursky Regional Healthcare Department
      • Moscow, Russian Federation
        • Moscow City Clinical Hospital #1 n.a.N.I.Pirogov
      • Moscow, Russian Federation
        • Moscow City Clinical Hospital #29 n.a.N.A.Bauman
      • Omsk, Russian Federation
        • Omsk Regional Clinical Oncology Center
      • Penza, Russian Federation
        • GBUZ "Penza Regional Clinical Hospital na N.N.Burdenko"
      • Ryazan, Russian Federation
        • City Clinical Hospital of Emergency Care
      • Saint Petersburg, Russian Federation
        • Hospital for War Veterans
      • Saint Petersburg, Russian Federation
        • Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
      • Saint Petersburg, Russian Federation
        • GBUZ 'Leningrad Regional Oncology Center'
      • Saint Petersburg, Russian Federation
        • GBUZ Leningrad Regional Clinical Hospital
      • Saint Petersburg, Russian Federation
        • North-West State Medical University named after I.I. Mechnikov
      • Saint Petersburg, Russian Federation
        • SPb GBUZ "City Hospital №26"
      • Saint Petersburg, Russian Federation
        • SPb GBUZ 'City Mariinskaya Hospital'
      • Tomsk, Russian Federation
        • Siberian State Medical University
      • Tomsk, Russian Federation
        • OGAUZ "Tomsk Regional Clinical Hospital"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Presence of signed informed consent for participation in the study.
  2. Men and women over 18 years of age (incl.).
  3. Demonstrated by one or several instrumental methods (ultrasound, cholangiography, CT or MRI) enlargement of intrahepatic bile ducts with visualized obturation of the main bile ducts caused by tumor.
  4. Duration of mechanical jaundice less than 30 days, including the first day of the screening period.
  5. The status by the classifications Eastern Cooperative Oncology Group (ECOG) scale is 0-2.
  6. Life expectancy of more than 3 months.
  7. Laboratory data corresponding to the following cutoff limits :

    hemoglobin ≥90 g / l; neutrophils ≥ 1.5x109 / l; Platelets ≥ 75 x 109 / L; AsAT and / or AlAT above 3 х normal but less than 25 х normal Serum creatinine not exceeding 2 × normal, Serum potassium within normal limits

  8. Negative urine test for pregnancy in women of reproductive age.
  9. For reproductive age: consent to use adequate methods of contraception or for complete abstinence from sexual activity for the period of the study.

Exclusion Criteria:

  1. Radical surgery planned within 10 days from the date of randomization.
  2. Liver metastases with the biliary block at the level of segmental ducts.
  3. Suspicion of metastases in the central nervous system or metastatic arachnoiditis during physical examination; clinically significant ascites.
  4. Acute destructive pancreatitis, diffuse peritonitis, ongoing bleeding of any etiology, sepsis (procalcitonin test of 10 ng / ml and above).
  5. Liver cirrhosis
  6. Presence of clinically significant cardiovascular diseases: chronic cardiac insufficiency III-IV functional class by NYHA, uncontrolled arterial hypertension, acute stroke or acute myocardial infarction in the previous 3 months, unstable angina, uncontrolled arrhythmia and severe heart rhythm disturbances.
  7. Pregnancy or lactation.
  8. Hypersensitivity to any component of the study drug / placebo and / or intolerance to any component of the study drug / placebo.
  9. Regular intake of medications prohibited or not permitted by the study protocol within 4 weeks prior to enrollment or medical indication tio start any medication prohibited or not permitted by the study protocol
  10. Concomitant chronic systemic immune or hormonal therapy.
  11. Gout.
  12. Alcohol and/or drug dependence.
  13. Active tuberculosis, HIV infection, syphilis, acute viral hepatitis.
  14. Any other conditions / diseases that may interfere with the patient's compliance with the requirements of the Protocol.
  15. Mental, physical and other reasons that do not allow the patient to comply with the requirements of the study protocol.
  16. Any other significant (by judgement of the investigator) condition that prevents the patient from entering the study.
  17. Participation in any clinical trial in the previous 3 months.
  18. Staff of the research center and their family members.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Remaxol® 400 ml + Placebo 400 ml
Treatment with Remaxol® 400 ml IV + Ringer solution 400 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Solution for intravenous infusions, containing succinate, methionine, inosine, and nicotinamide in 400 ml glass bottle
Other Names:
  • Remaxol (succinate + methionine + inosine + nicotinamide)
Solution for intravenous infusion, 400 or 800 ml
Other Names:
  • Placebo
Experimental: Remaxol® 800 ml
Treatment with Remaxol® 800 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Solution for intravenous infusions, containing succinate, methionine, inosine, and nicotinamide in 400 ml glass bottle
Other Names:
  • Remaxol (succinate + methionine + inosine + nicotinamide)
Placebo Comparator: Control
Treatment with Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution
Solution for intravenous infusion, 400 or 800 ml
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to regression of jaundice
Time Frame: 21 days
The time (days) from the day of the drainage operation to the reduction of the total bilirubin level down to 90 μmol / l, in experimental (Remaxol®) vs. control (Placebo) groups
21 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Regression of cytolysis (normal alanine aminotransferase and aspartate aminotransferase serum levels)
Time Frame: 11 days
Proportion of patients in study groups who reached normal serum levels of alanine aminotransferase and aspartate aminotransferase on day 11 from the start of treatment
11 days
Regression of cholestasis
Time Frame: 11 days
Proportion of patients in study groups who reached normal serum levels of alkaline phosphatase, GGTP, total bilirubin, and direct bilirubin on day 11 from the start of treatment
11 days
Regression of encephalopathy
Time Frame: 11 days
Proportion of patients in study groups who had normal brain functioning on day 11, as reflected by the neurophysiological test for the evaluation of the degree of encephalopathy
11 days
Serum bilirubin
Time Frame: 21 days
Dynamics of total and direct bilirubin serum levels against baseline values and between visits in the study groups
21 days
Serum alkaline phosphatase
Time Frame: 21 days
Dynamics of serum alkaline phosphatase level against baseline values and between visits in the study groups
21 days
Serum GGTP
Time Frame: 21 days
Dynamics of serum gamma-glutamyltranspeptidase level against baseline values and between visits in the study groups
21 days
Serum alanine aminotransferase
Time Frame: 21 days
Dynamics of serum alanine aminotransferase level against baseline values and between visits in the study groups
21 days
Serum aspartate aminotransferase
Time Frame: 21 days
Dynamics of serum aspartate aminotransferase level against baseline values and between visits in the study groups
21 days
Liver function
Time Frame: 21 days
State of liver protein synthesis function (as reflected by serum levels of total protein, albumin, INR, PT, PTI, APTT, fibrinogen) against baseline values and/or between visits
21 days
Kidney function
Time Frame: 21 days
State of kidney function (creatinine serum level) against baseline values and/or between visits
21 days
Proportion of patients with complications of jaundice
Time Frame: 21 days
The number of patients in the study groups who developed complications in the postoperative period which were, according to the researcher's assessment, causally related to the obstructive jaundice (for example, purulent cholangitis, sepsis, kidney failure)
21 days
Eastern Cooperative Oncology Group (ECOG) Performance Status
Time Frame: 31 days

Status of patients in the study groups by ECOG (Eastern Cooperative Oncology Group) grades at the end of the study. ECOG Performance Status consists of the following grades:

0 - fully active, able to carry on all pre-disease performance without restriction;

  1. - restricted but ambulatory and able to carry out work of a light or sedentary nature;
  2. - ambulatory and capable of all selfcare but unable to carry out any work activities;
  3. - capable of only limited selfcare; partially confined to bed or chair;
  4. - completely disabled; cannot carry on any selfcare;
  5. - Dead
31 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Mikhail S. Bogomolov, MD, PhD, St. Petersburg State Medical University n.a. I.P.Pavlov

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 3, 2017

Primary Completion (Actual)

February 3, 2020

Study Completion (Actual)

March 4, 2020

Study Registration Dates

First Submitted

January 23, 2018

First Submitted That Met QC Criteria

January 29, 2018

First Posted (Actual)

January 30, 2018

Study Record Updates

Last Update Posted (Actual)

July 10, 2020

Last Update Submitted That Met QC Criteria

July 9, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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