Back to resultsRemaxol® in Malignant Mechanical Jaundice
Primary Purpose
Jaundice; Malignant
Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Remaxol®
Ringer's Solution
Sponsored by
About this trial
This is an interventional treatment trial for Jaundice; Malignant focused on measuring Jaundice, obstructive, Methionine, Succinic acid
Eligibility Criteria
Inclusion Criteria:
- Presence of signed informed consent for participation in the study.
- Men and women over 18 years of age (incl.).
- 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.
- Duration of mechanical jaundice less than 30 days, including the first day of the screening period.
- The status by the classifications Eastern Cooperative Oncology Group (ECOG) scale is 0-2.
- Life expectancy of more than 3 months.
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
- Negative urine test for pregnancy in women of reproductive age.
- 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:
- Radical surgery planned within 10 days from the date of randomization.
- Liver metastases with the biliary block at the level of segmental ducts.
- Suspicion of metastases in the central nervous system or metastatic arachnoiditis during physical examination; clinically significant ascites.
- Acute destructive pancreatitis, diffuse peritonitis, ongoing bleeding of any etiology, sepsis (procalcitonin test of 10 ng / ml and above).
- Liver cirrhosis
- 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.
- Pregnancy or lactation.
- Hypersensitivity to any component of the study drug / placebo and / or intolerance to any component of the study drug / placebo.
- 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
- Concomitant chronic systemic immune or hormonal therapy.
- Gout.
- Alcohol and/or drug dependence.
- Active tuberculosis, HIV infection, syphilis, acute viral hepatitis.
- Any other conditions / diseases that may interfere with the patient's compliance with the requirements of the Protocol.
- Mental, physical and other reasons that do not allow the patient to comply with the requirements of the study protocol.
- Any other significant (by judgement of the investigator) condition that prevents the patient from entering the study.
- Participation in any clinical trial in the previous 3 months.
- Staff of the research center and their family members.
Sites / Locations
- GBUZ 'Bryansk City Hospital #1'
- Regional Clinical Hospital of Emergency Care n.a.M.A.Podgorbunsky
- KBUZ 'Regional Clinical Hospital'
- OBUZ 'Kursy Regional Clinical Oncology Dispensary' of Kursky Regional Healthcare Department
- Moscow City Clinical Hospital #1 n.a.N.I.Pirogov
- Moscow City Clinical Hospital #29 n.a.N.A.Bauman
- Omsk Regional Clinical Oncology Center
- GBUZ "Penza Regional Clinical Hospital na N.N.Burdenko"
- City Clinical Hospital of Emergency Care
- GBUZ 'Leningrad Regional Oncology Center'
- GBUZ Leningrad Regional Clinical Hospital
- Hospital for War Veterans
- North-West State Medical University named after I.I. Mechnikov
- Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
- SPb GBUZ "City Hospital №26"
- SPb GBUZ 'City Mariinskaya Hospital'
- OGAUZ "Tomsk Regional Clinical Hospital"
- Siberian State Medical University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Remaxol® 400 ml + Placebo 400 ml
Remaxol® 800 ml
Control
Arm Description
Treatment with Remaxol® 400 ml IV + Ringer solution 400 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Treatment with Remaxol® 800 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Treatment with Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution
Outcomes
Primary Outcome Measures
Time to regression of jaundice
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
Regression of cytolysis (normal alanine aminotransferase and aspartate aminotransferase serum levels)
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
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
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
Dynamics of total and direct bilirubin serum levels against baseline values and between visits in the study groups
Serum alkaline phosphatase
Dynamics of serum alkaline phosphatase level against baseline values and between visits in the study groups
Serum GGTP
Dynamics of serum gamma-glutamyltranspeptidase level against baseline values and between visits in the study groups
Serum alanine aminotransferase
Dynamics of serum alanine aminotransferase level against baseline values and between visits in the study groups
Serum aspartate aminotransferase
Dynamics of serum aspartate aminotransferase level against baseline values and between visits in the study groups
Liver function
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
State of kidney function (creatinine serum level) against baseline values and/or between visits
Proportion of patients with complications of jaundice
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
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;
- restricted but ambulatory and able to carry out work of a light or sedentary nature;
- ambulatory and capable of all selfcare but unable to carry out any work activities;
- capable of only limited selfcare; partially confined to bed or chair;
- completely disabled; cannot carry on any selfcare;
- Dead
Full Information
NCT ID
NCT03416062
First Posted
January 23, 2018
Last Updated
July 9, 2020
Sponsor
POLYSAN Scientific & Technological Pharmaceutical Company
1. Study Identification
Unique Protocol Identification Number
NCT03416062
Brief Title
Remaxol® in Malignant Mechanical Jaundice
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
April 3, 2017 (Actual)
Primary Completion Date
February 3, 2020 (Actual)
Study Completion Date
March 4, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
POLYSAN Scientific & Technological Pharmaceutical Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Jaundice; Malignant
Keywords
Jaundice, obstructive, Methionine, Succinic acid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
240 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Remaxol® 400 ml + Placebo 400 ml
Arm Type
Experimental
Arm Description
Treatment with Remaxol® 400 ml IV + Ringer solution 400 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Arm Title
Remaxol® 800 ml
Arm Type
Experimental
Arm Description
Treatment with Remaxol® 800 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Treatment with Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution
Intervention Type
Drug
Intervention Name(s)
Remaxol®
Other Intervention Name(s)
Remaxol (succinate + methionine + inosine + nicotinamide)
Intervention Description
Solution for intravenous infusions, containing succinate, methionine, inosine, and nicotinamide in 400 ml glass bottle
Intervention Type
Drug
Intervention Name(s)
Ringer's Solution
Other Intervention Name(s)
Placebo
Intervention Description
Solution for intravenous infusion, 400 or 800 ml
Primary Outcome Measure Information:
Title
Time to regression of jaundice
Description
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
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Regression of cytolysis (normal alanine aminotransferase and aspartate aminotransferase serum levels)
Description
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
Time Frame
11 days
Title
Regression of cholestasis
Description
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
Time Frame
11 days
Title
Regression of encephalopathy
Description
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
Time Frame
11 days
Title
Serum bilirubin
Description
Dynamics of total and direct bilirubin serum levels against baseline values and between visits in the study groups
Time Frame
21 days
Title
Serum alkaline phosphatase
Description
Dynamics of serum alkaline phosphatase level against baseline values and between visits in the study groups
Time Frame
21 days
Title
Serum GGTP
Description
Dynamics of serum gamma-glutamyltranspeptidase level against baseline values and between visits in the study groups
Time Frame
21 days
Title
Serum alanine aminotransferase
Description
Dynamics of serum alanine aminotransferase level against baseline values and between visits in the study groups
Time Frame
21 days
Title
Serum aspartate aminotransferase
Description
Dynamics of serum aspartate aminotransferase level against baseline values and between visits in the study groups
Time Frame
21 days
Title
Liver function
Description
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
Time Frame
21 days
Title
Kidney function
Description
State of kidney function (creatinine serum level) against baseline values and/or between visits
Time Frame
21 days
Title
Proportion of patients with complications of jaundice
Description
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)
Time Frame
21 days
Title
Eastern Cooperative Oncology Group (ECOG) Performance Status
Description
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;
- restricted but ambulatory and able to carry out work of a light or sedentary nature;
- ambulatory and capable of all selfcare but unable to carry out any work activities;
- capable of only limited selfcare; partially confined to bed or chair;
- completely disabled; cannot carry on any selfcare;
- Dead
Time Frame
31 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Presence of signed informed consent for participation in the study.
Men and women over 18 years of age (incl.).
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.
Duration of mechanical jaundice less than 30 days, including the first day of the screening period.
The status by the classifications Eastern Cooperative Oncology Group (ECOG) scale is 0-2.
Life expectancy of more than 3 months.
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
Negative urine test for pregnancy in women of reproductive age.
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:
Radical surgery planned within 10 days from the date of randomization.
Liver metastases with the biliary block at the level of segmental ducts.
Suspicion of metastases in the central nervous system or metastatic arachnoiditis during physical examination; clinically significant ascites.
Acute destructive pancreatitis, diffuse peritonitis, ongoing bleeding of any etiology, sepsis (procalcitonin test of 10 ng / ml and above).
Liver cirrhosis
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.
Pregnancy or lactation.
Hypersensitivity to any component of the study drug / placebo and / or intolerance to any component of the study drug / placebo.
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
Concomitant chronic systemic immune or hormonal therapy.
Gout.
Alcohol and/or drug dependence.
Active tuberculosis, HIV infection, syphilis, acute viral hepatitis.
Any other conditions / diseases that may interfere with the patient's compliance with the requirements of the Protocol.
Mental, physical and other reasons that do not allow the patient to comply with the requirements of the study protocol.
Any other significant (by judgement of the investigator) condition that prevents the patient from entering the study.
Participation in any clinical trial in the previous 3 months.
Staff of the research center and their family members.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikhail S. Bogomolov, MD, PhD
Organizational Affiliation
St. Petersburg State Medical University n.a. I.P.Pavlov
Official's Role
Study Director
Facility Information:
Facility Name
GBUZ 'Bryansk City Hospital #1'
City
Bryansk
Country
Russian Federation
Facility Name
Regional Clinical Hospital of Emergency Care n.a.M.A.Podgorbunsky
City
Kemerovo
Country
Russian Federation
Facility Name
KBUZ 'Regional Clinical Hospital'
City
Krasnoyarsk
Country
Russian Federation
Facility Name
OBUZ 'Kursy Regional Clinical Oncology Dispensary' of Kursky Regional Healthcare Department
City
Kursk
Country
Russian Federation
Facility Name
Moscow City Clinical Hospital #1 n.a.N.I.Pirogov
City
Moscow
Country
Russian Federation
Facility Name
Moscow City Clinical Hospital #29 n.a.N.A.Bauman
City
Moscow
Country
Russian Federation
Facility Name
Omsk Regional Clinical Oncology Center
City
Omsk
Country
Russian Federation
Facility Name
GBUZ "Penza Regional Clinical Hospital na N.N.Burdenko"
City
Penza
Country
Russian Federation
Facility Name
City Clinical Hospital of Emergency Care
City
Ryazan
Country
Russian Federation
Facility Name
GBUZ 'Leningrad Regional Oncology Center'
City
Saint Petersburg
Country
Russian Federation
Facility Name
GBUZ Leningrad Regional Clinical Hospital
City
Saint Petersburg
Country
Russian Federation
Facility Name
Hospital for War Veterans
City
Saint Petersburg
Country
Russian Federation
Facility Name
North-West State Medical University named after I.I. Mechnikov
City
Saint Petersburg
Country
Russian Federation
Facility Name
Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
City
Saint Petersburg
Country
Russian Federation
Facility Name
SPb GBUZ "City Hospital №26"
City
Saint Petersburg
Country
Russian Federation
Facility Name
SPb GBUZ 'City Mariinskaya Hospital'
City
Saint Petersburg
Country
Russian Federation
Facility Name
OGAUZ "Tomsk Regional Clinical Hospital"
City
Tomsk
Country
Russian Federation
Facility Name
Siberian State Medical University
City
Tomsk
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Remaxol® in Malignant Mechanical Jaundice
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