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Remaxol® in Malignant Mechanical Jaundice

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ClinicalTrials.gov Identifier: NCT03416062
Recruitment Status : Recruiting
First Posted : January 30, 2018
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
POLYSAN Scientific & Technological Pharmaceutical Company

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Jaundice; Malignant Drug: Remaxol® Drug: Ringer's Solution Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 288 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 3, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


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)
Drug: Remaxol®
Solution for intravenous infusions, containing succinate, methionine, inosine, and nicotinamide in 400 ml glass bottle
Other Name: Remaxol (succinate + methionine + inosine + nicotinamide)

Drug: Ringer's Solution
Solution for intravenous infusion, 400 or 800 ml
Other Name: Placebo

Experimental: Remaxol® 800 ml
Treatment with Remaxol® 800 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Drug: Remaxol®
Solution for intravenous infusions, containing succinate, methionine, inosine, and nicotinamide in 400 ml glass bottle
Other Name: Remaxol (succinate + methionine + inosine + nicotinamide)

Placebo Comparator: Control
Treatment with Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution
Drug: Ringer's Solution
Solution for intravenous infusion, 400 or 800 ml
Other Name: Placebo




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Serum bilirubin [ Time Frame: 21 days ]
    Dynamics of total and direct bilirubin serum levels against baseline values and between visits in the study groups

  5. Serum alkaline phosphatase [ Time Frame: 21 days ]
    Dynamics of serum alkaline phosphatase level against baseline values and between visits in the study groups

  6. Serum GGTP [ Time Frame: 21 days ]
    Dynamics of serum gamma-glutamyltranspeptidase level against baseline values and between visits in the study groups

  7. Serum alanine aminotransferase [ Time Frame: 21 days ]
    Dynamics of serum alanine aminotransferase level against baseline values and between visits in the study groups

  8. Serum aspartate aminotransferase [ Time Frame: 21 days ]
    Dynamics of serum aspartate aminotransferase level against baseline values and between visits in the study groups

  9. 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

  10. Kidney function [ Time Frame: 21 days ]
    State of kidney function (creatinine serum level) against baseline values and/or between visits

  11. 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)

  12. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03416062


Contacts
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Contact: Aleksey \ L Kovalenko, Doc Biol Sci +78127108225 ext 212 science@polysan.ru

Locations
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Russian Federation
GBUZ 'Bryansk City Hospital #1' Recruiting
Bryansk, Russian Federation
Contact: Alexey K. Vorontsov         
Regional Clinical Hospital of Emergency Care n.a.M.A.Podgorbunsky Recruiting
Kemerovo, Russian Federation
Contact: Vladimir V. Pavlenko         
KBUZ 'Regional Clinical Hospital' Recruiting
Krasnoyarsk, Russian Federation
Contact: Alexey I. Gritsan         
OBUZ 'Kursy Regional Clinical Oncology Dispensary' of Kursky Regional Healthcare Department Recruiting
Kursk, Russian Federation
Contact: Igor D. Lifirenko         
Moscow City Clinical Hospital #1 n.a.N.I.Pirogov Recruiting
Moscow, Russian Federation
Contact: Kamil D. Dalgatov         
Moscow City Clinical Hospital #29 n.a.N.A.Bauman Recruiting
Moscow, Russian Federation
Contact: Maxim R. Kuznetsov         
Omsk Regional Clinical Oncology Center Recruiting
Omsk, Russian Federation
Contact: Viktor A Tsarkov         
GBUZ "Penza Regional Clinical Hospital na N.N.Burdenko" Recruiting
Penza, Russian Federation
Contact: Alexandr V. Klimashevich         
City Clinical Hospital of Emergency Care Recruiting
Ryazan, Russian Federation
Contact: Alexandr A. Kopeikin         
GBUZ 'Leningrad Regional Oncology Center' Recruiting
Saint Petersburg, Russian Federation
Contact: Kirill G. Shostka         
GBUZ Leningrad Regional Clinical Hospital Recruiting
Saint Petersburg, Russian Federation
Contact: Andrey S. Pryadko         
Hospital for War Veterans Recruiting
Saint Petersburg, Russian Federation
Contact: Georgy A. Belekhov         
North-West State Medical University named after I.I. Mechnikov Recruiting
Saint Petersburg, Russian Federation
Contact: Eldar E Topuzov         
Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine Recruiting
Saint Petersburg, Russian Federation
Contact: Anton S. Povzun         
SPb GBUZ "City Hospital №26" Recruiting
Saint Petersburg, Russian Federation
Contact: Elena L Belyaeva         
SPb GBUZ 'City Mariinskaya Hospital' Recruiting
Saint Petersburg, Russian Federation
Contact: Yuriy A. Spesivtsev         
OGAUZ "Tomsk Regional Clinical Hospital" Recruiting
Tomsk, Russian Federation
Contact: Ludmila G. Lenskaya         
Siberian State Medical University Recruiting
Tomsk, Russian Federation
Contact: Igor Yu. Klinovitsky         
Sponsors and Collaborators
POLYSAN Scientific & Technological Pharmaceutical Company
Investigators
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Study Director: Mikhail S. Bogomolov, MD, PhD St. Petersburg State Medical University n.a. I.P.Pavlov

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Responsible Party: POLYSAN Scientific & Technological Pharmaceutical Company
ClinicalTrials.gov Identifier: NCT03416062     History of Changes
Other Study ID Numbers: REM-CJ-III-16
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by POLYSAN Scientific & Technological Pharmaceutical Company:
Jaundice, obstructive
Methionine
Succinic acid

Additional relevant MeSH terms:
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Jaundice
Jaundice, Obstructive
Hyperbilirubinemia
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Pharmaceutical Solutions
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents