Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Remaxol® in Malignant Mechanical Jaundice

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
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

Tracking Information
First Submitted Date  ICMJE January 23, 2018
First Posted Date  ICMJE January 30, 2018
Last Update Posted Date February 12, 2019
Actual Study Start Date  ICMJE April 3, 2017
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03416062 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2018)
  • 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
  • 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
  • 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
  • Serum bilirubin [ Time Frame: 21 days ]
    Dynamics of total and direct bilirubin serum levels against baseline values and between visits in the study groups
  • Serum alkaline phosphatase [ Time Frame: 21 days ]
    Dynamics of serum alkaline phosphatase level against baseline values and between visits in the study groups
  • Serum GGTP [ Time Frame: 21 days ]
    Dynamics of serum gamma-glutamyltranspeptidase level against baseline values and between visits in the study groups
  • Serum alanine aminotransferase [ Time Frame: 21 days ]
    Dynamics of serum alanine aminotransferase level against baseline values and between visits in the study groups
  • Serum aspartate aminotransferase [ Time Frame: 21 days ]
    Dynamics of serum aspartate aminotransferase level against baseline values and between visits in the study groups
  • 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
  • Kidney function [ Time Frame: 21 days ]
    State of kidney function (creatinine serum level) against baseline values and/or between visits
  • 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)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2018)
  • 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
  • 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
  • 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
  • Serum biochemistry [ Time Frame: 21 days ]
    Dynamics of total and direct bilirubin serum levels, level of alkaline phosphatase and GGTP against baseline values and between visits in the study groups
  • Serum alanine aminotransferase and aspartate aminotransferase [ Time Frame: 21 days ]
    Dynamics of serum alanine aminotransferase and aspartate aminotransferase against baseline values and between visits in the study groups
  • 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
  • Lipids and carbohydrates metabolism [ Time Frame: 21 days ]
    State of lipid and carbohydrate metabolism (serum levels of total cholesterol, triglycerides, lipoproteins, glucose, amylase) against baseline values and/or between visits
  • Kidney function [ Time Frame: 21 days ]
    State of kidney function (urea level, creatinine level, and creatinine clearance) against baseline values and/or between visits
  • 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)
  • ECOG [ Time Frame: 31 days ]
    Status of patients in the study groups on the ECOG scale at the end of the study
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Remaxol® in Malignant Mechanical Jaundice
Official Title  ICMJE 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
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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Jaundice; Malignant
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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)
    Interventions:
    • Drug: Remaxol®
    • Drug: Ringer's Solution
  • Experimental: Remaxol® 800 ml
    Treatment with Remaxol® 800 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
    Intervention: Drug: Remaxol®
  • Placebo Comparator: Control
    Treatment with Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution
    Intervention: Drug: Ringer's Solution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 29, 2018)
288
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2019
Estimated Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Aleksey \ L Kovalenko, Doc Biol Sci +78127108225 ext 212 science@polysan.ru
Listed Location Countries  ICMJE Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03416062
Other Study ID Numbers  ICMJE REM-CJ-III-16
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party POLYSAN Scientific & Technological Pharmaceutical Company
Study Sponsor  ICMJE POLYSAN Scientific & Technological Pharmaceutical Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Mikhail S. Bogomolov, MD, PhD St. Petersburg State Medical University n.a. I.P.Pavlov
PRS Account POLYSAN Scientific & Technological Pharmaceutical Company
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP