Back to resultsRemaxol® in Mechanical Jaundice of Non-malignant Origin
Primary Purpose
Jaundice, Obstructive
Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Remaxol (succinate + methionine + inosine + nicotinamide)
Ringer's Solution
Sponsored by
About this trial
This is an interventional treatment trial for Jaundice, Obstructive focused on measuring obstructive jaundice, non-malignant, mechanical jaundice, non-malignant, Methionine, Succinic acid
Eligibility Criteria
Inclusion Criteria:
- Presence of signed informed consent for participation in the study.
- Men and women over the age of 18 (incl.).
- Obstructive jaundice, verified by enlargement of intrahepatic bile ducts with proven non-tumor obstruction of extrahepatic bile ducts.
- Duration of mechanical jaundice 15 days or less.
- The level of total bilirubin in the blood from 5-fold to 20-fold exceeding normal.
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 20 х normal
- Serum creatinine not exceeding 2 × normal,
- Serum potassium within normal limits
- Negative urine test for pregnancy in women of reproductive age.
- Consent to use adequate methods of contraception or for complete abstinence from sexual activity for the period of the study.
- Consent to abstain completely from alcohol intake during the study period.
Exclusion Criteria:
- Tumor causing the obstruction of the bile ducts or the presence of any other malignancy at the time of randomization.
- The need for another radical surgery within 2 weeks from the planned date of randomization.
- Acute destructive pancreatitis, diffuse or diffuse peritonitis, sepsis.
- Preexisting liver cirrhosis.
- Exacerbation of the chronic peptic ulcer.
- Ongoing bleeding.
- 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.
- Any other decompensated disease.
- Pregnancy or lactation.
- Hypersensitivity to any component of the study drug / placebo and / or intolerance to any component of the study drug / placebo.
- Regular admission of medications prohibited or not permitted by the study protocol within 4 weeks prior to enrollment.
- 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
- Moscow 'City Clinical Hospital #24
- Moscow City Clinical Hospital #1 n.a.N.I.Pirogov
- Moscow City Clinical Hospital #29 n.a.N.A.Bauman
- Moscow City Clinical Hospital #67 n.a. L.A.Vorohobova
- Novosibirsk State Medical University
- City Clinical Hospital of Emergency Care
- North-West State Medical University named after I.I. Mechnikov
- State Budgetary Health Care Institution "City Hospital № 26"
- Hospital for War Veterans
- Leningrad Regional Clinical Hospital
- Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
- City Clinical Hospital #3 n.a.B.I.Alperovich
- GBUZ YO 'Regional Clinical Hospital'
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Remaxol 400 ml
Remaxol 800 ml
Control
Arm Description
Group I: treatment with Remaxol 400 ml IV + Ringer solution 400 ml IV for 7 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Group II: treatment with Remaxol 800 ml IV for 7 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Group III: Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution
Outcomes
Primary Outcome Measures
Days to regression of jaundice
Time (days) from the date of drainage surgery to the reduction of the total bilirubin level down to 50 μmol / l, in experimental (Remaxol®) and control (Placebo) groups
Secondary Outcome Measures
Disappearance of cytolysis (normal alanine aminotransferase and aspartate aminotransferase serum levels) on day 5
Proportion of patients in study groups who reached normal serum levels of alanine aminotransferase and aspartate aminotransferase on day 5 from the start of treatment
Disappearance of cholestasis on day 5
Proportion of patients in study groups who reached normal serum levels of alkaline phosphatase, GGTP, total bilirubin, and direct bilirubin on day 5 from the start of treatment
Disappearance of encephalopathy on day 5
Proportion of patients in study groups who had normal brain functioning on day 5, 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 enzymes
Dynamics of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and GGTP 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, fibrinogen) against baseline values and/or between visits
Kidney function
State of kidney function (serum creatinine) 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).
Full Information
NCT ID
NCT03418935
First Posted
January 19, 2018
Last Updated
July 10, 2020
Sponsor
POLYSAN Scientific & Technological Pharmaceutical Company
1. Study Identification
Unique Protocol Identification Number
NCT03418935
Brief Title
Remaxol® in Mechanical Jaundice of Non-malignant Origin
Official Title
A Multicenter, Double-Blind, Placebo-Controlled, Randomized Trial of Efficacy and Safety of Remaxol®, a Solution for Intravenous Infusions Produced by STPF "POLYSAN" (Russia), in Patients With Mechanical Jaundice of Non-Malignant Origin
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
March 31, 2020 (Actual)
Study Completion Date
April 13, 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 purpose of this study is to assess the safety and efficacy of Remaxol (succinate + methionine + inosine + nicotinamide; POLYSAN Ltd., Russia) infusions at dose 400 and 800 ml to treat mechanical jaundice of non-tumor cause during the first week after surgery.
Detailed Description
The study will be performed in in-hospital patients with obstructive jaundice cause by conditions other than tumor (predominantly by cholelithiasis; ICD-10 codes K80 and K83.1). The patients will be screened in the 15 days preceeding the appointed drainage surgery. The treatment will be started in the first 6 hours after the drainage surgery and continue for 7 days.
Following screening, patients who meet the inclusion criteria and have no criteria for exclusion will be randomly assigned into three study groups in the proportion of 1: 1: 1):
Group I: treatment with Remaxol 400 ml IV + Ringer solution 400 ml IV for 7 days.
Group II: treatment with Remaxol 800 ml IV for 7 days. Group III (control): Ringer solution 800 ml IV for 7 days.
Physical examination data, vital signs, biochemistry panel (including bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, GGTP) will be assessed on days 1-8, on day 11 and day 14.
Diagnostic abdominal ultrasound will be performed before surgery and on days 3 and 8.
Neurophysiological test for the evaluation of the degree of encephalopathy will be performed before surgery, on days 3, 5, 8, and 14.
All patients will be followed up for 14 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Jaundice, Obstructive
Keywords
obstructive jaundice, non-malignant, mechanical jaundice, non-malignant, Methionine, Succinic acid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
342 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Remaxol 400 ml
Arm Type
Experimental
Arm Description
Group I: treatment with Remaxol 400 ml IV + Ringer solution 400 ml IV for 7 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Arm Title
Remaxol 800 ml
Arm Type
Experimental
Arm Description
Group II: treatment with Remaxol 800 ml IV for 7 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Group III: Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution
Intervention Type
Drug
Intervention Name(s)
Remaxol (succinate + methionine + inosine + nicotinamide)
Other Intervention Name(s)
Remaxol®
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
Intravenous infusion, 400 or 800 ml
Primary Outcome Measure Information:
Title
Days to regression of jaundice
Description
Time (days) from the date of drainage surgery to the reduction of the total bilirubin level down to 50 μmol / l, in experimental (Remaxol®) and control (Placebo) groups
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Disappearance of cytolysis (normal alanine aminotransferase and aspartate aminotransferase serum levels) on day 5
Description
Proportion of patients in study groups who reached normal serum levels of alanine aminotransferase and aspartate aminotransferase on day 5 from the start of treatment
Time Frame
5 days
Title
Disappearance of cholestasis on day 5
Description
Proportion of patients in study groups who reached normal serum levels of alkaline phosphatase, GGTP, total bilirubin, and direct bilirubin on day 5 from the start of treatment
Time Frame
5 days
Title
Disappearance of encephalopathy on day 5
Description
Proportion of patients in study groups who had normal brain functioning on day 5, as reflected by the neurophysiological test for the evaluation of the degree of encephalopathy
Time Frame
5 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
14 days
Title
Serum enzymes
Description
Dynamics of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and GGTP against baseline values and between visits in the study groups
Time Frame
14 days
Title
Liver function
Description
State of liver protein synthesis function (as reflected by serum levels of total protein, albumin, fibrinogen) against baseline values and/or between visits
Time Frame
14 days
Title
Kidney function
Description
State of kidney function (serum creatinine) against baseline values and/or between visits
Time Frame
14 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
14 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 the age of 18 (incl.).
Obstructive jaundice, verified by enlargement of intrahepatic bile ducts with proven non-tumor obstruction of extrahepatic bile ducts.
Duration of mechanical jaundice 15 days or less.
The level of total bilirubin in the blood from 5-fold to 20-fold exceeding normal.
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 20 х normal
Serum creatinine not exceeding 2 × normal,
Serum potassium within normal limits
Negative urine test for pregnancy in women of reproductive age.
Consent to use adequate methods of contraception or for complete abstinence from sexual activity for the period of the study.
Consent to abstain completely from alcohol intake during the study period.
Exclusion Criteria:
Tumor causing the obstruction of the bile ducts or the presence of any other malignancy at the time of randomization.
The need for another radical surgery within 2 weeks from the planned date of randomization.
Acute destructive pancreatitis, diffuse or diffuse peritonitis, sepsis.
Preexisting liver cirrhosis.
Exacerbation of the chronic peptic ulcer.
Ongoing bleeding.
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.
Any other decompensated disease.
Pregnancy or lactation.
Hypersensitivity to any component of the study drug / placebo and / or intolerance to any component of the study drug / placebo.
Regular admission of medications prohibited or not permitted by the study protocol within 4 weeks prior to enrollment.
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
Moscow 'City Clinical Hospital #24
City
Moscow
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
Moscow City Clinical Hospital #67 n.a. L.A.Vorohobova
City
Moscow
Country
Russian Federation
Facility Name
Novosibirsk State Medical University
City
Novosibirsk
Country
Russian Federation
Facility Name
City Clinical Hospital of Emergency Care
City
Ryazan
Country
Russian Federation
Facility Name
North-West State Medical University named after I.I. Mechnikov
City
Saint Petersburg
ZIP/Postal Code
191015
Country
Russian Federation
Facility Name
State Budgetary Health Care Institution "City Hospital № 26"
City
Saint Petersburg
ZIP/Postal Code
196247
Country
Russian Federation
Facility Name
Hospital for War Veterans
City
Saint Petersburg
Country
Russian Federation
Facility Name
Leningrad Regional Clinical Hospital
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
City Clinical Hospital #3 n.a.B.I.Alperovich
City
Tomsk
Country
Russian Federation
Facility Name
GBUZ YO 'Regional Clinical Hospital'
City
Yaroslavl
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Remaxol® in Mechanical Jaundice of Non-malignant Origin
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