CClinicalTrials.gg
CompletedNCT03416062Updated Jul 10, 2020

Remaxol® in Malignant Mechanical Jaundice

A Phase 3 interventional study of Remaxol® and Ringer's Solution in Jaundice; Malignant, sponsored by POLYSAN Scientific & Technological Pharmaceutical Company. Completed at 18 sites in Russian Federation. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-10.

Sponsored by POLYSAN Scientific & Technological Pharmaceutical Company · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
240
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Jaundice; Malignant

Keywords

  • Jaundice, obstructive
  • Methionine
  • Succinic acid
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
240 participants (actual)

Study arms

  • 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® · Drug: Ringer's Solution

  • Experimental
    Remaxol® 800 ml

    Treatment with Remaxol® 800 ml IV for 10 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)

    Drug: Remaxol®

  • Placebo comparator
    Control

    Treatment with Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution

    Drug: Ringer's Solution

Interventions

  • DrugRemaxol®

    Solution for intravenous infusions, containing succinate, methionine, inosine, and nicotinamide in 400 ml glass bottle

    Also known as: Remaxol (succinate + methionine + inosine + nicotinamide)

  • DrugRinger's Solution

    Solution for intravenous infusion, 400 or 800 ml

    Also known as: Placebo

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: 21 days

Secondary outcomes

  1. 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

    Time frame: 11 days

  2. 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

    Time frame: 11 days

  3. 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

    Time frame: 11 days

  4. Serum bilirubin

    Dynamics of total and direct bilirubin serum levels against baseline values and between visits in the study groups

    Time frame: 21 days

  5. Serum alkaline phosphatase

    Dynamics of serum alkaline phosphatase level against baseline values and between visits in the study groups

    Time frame: 21 days

  6. Serum GGTP

    Dynamics of serum gamma-glutamyltranspeptidase level against baseline values and between visits in the study groups

    Time frame: 21 days

  7. Serum alanine aminotransferase

    Dynamics of serum alanine aminotransferase level against baseline values and between visits in the study groups

    Time frame: 21 days

  8. Serum aspartate aminotransferase

    Dynamics of serum aspartate aminotransferase level against baseline values and between visits in the study groups

    Time frame: 21 days

  9. 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

    Time frame: 21 days

  10. Kidney function

    State of kidney function (creatinine serum level) against baseline values and/or between visits

    Time frame: 21 days

  11. 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)

    Time frame: 21 days

  12. 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; 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

    Time frame: 31 days

06

Study locations

18 sites
  • GBUZ 'Bryansk City Hospital #1'
    Bryansk, Russian Federation
  • Regional Clinical Hospital of Emergency Care n.a.M.A.Podgorbunsky
    Kemerovo, Russian Federation
  • KBUZ 'Regional Clinical Hospital'
    Krasnoyarsk, Russian Federation
  • OBUZ 'Kursy Regional Clinical Oncology Dispensary' of Kursky Regional Healthcare Department
    Kursk, 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
    Moscow, Russian Federation
  • Omsk Regional Clinical Oncology Center
    Omsk, Russian Federation
  • GBUZ "Penza Regional Clinical Hospital na N.N.Burdenko"
    Penza, Russian Federation
  • City Clinical Hospital of Emergency Care
    Ryazan, Russian Federation
  • GBUZ 'Leningrad Regional Oncology Center'
    Saint Petersburg, Russian Federation
  • GBUZ Leningrad Regional Clinical Hospital
    Saint Petersburg, Russian Federation
  • Hospital for War Veterans
    Saint Petersburg, Russian Federation
  • North-West State Medical University named after I.I. Mechnikov
    Saint Petersburg, Russian Federation
  • Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
    Saint Petersburg, Russian Federation
  • SPb GBUZ "City Hospital №26"
    Saint Petersburg, Russian Federation
  • SPb GBUZ 'City Mariinskaya Hospital'
    Saint Petersburg, Russian Federation
  • OGAUZ "Tomsk Regional Clinical Hospital"
    Tomsk, Russian Federation
  • Siberian State Medical University
    Tomsk, Russian Federation
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03416062
Lead sponsor
POLYSAN Scientific & Technological Pharmaceutical Company
Responsible party
Sponsor
First posted
Jan 30, 2018
Start date
Apr 3, 2017
Primary completion
Feb 3, 2020
Completion
Mar 4, 2020
Last update
Jul 10, 2020

Study contacts

Mikhail S. Bogomolov, MD, PhD
study director · St. Petersburg State Medical University n.a. I.P.Pavlov

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2020. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion