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CompletedNCT03418935Updated Jul 14, 2020

Remaxol® in Mechanical Jaundice of Non-malignant Origin

A Phase 3 interventional study of Remaxol (succinate + methionine + inosine + nicotinamide) and Ringer's Solution in Jaundice, Obstructive, sponsored by POLYSAN Scientific & Technological Pharmaceutical Company. Completed at 13 sites in Russian Federation. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-14.

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

Phase
Phase 3
Study type
Interventional
Enrollment
342
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Jaundice, Obstructive

Keywords

  • obstructive jaundice, non-malignant
  • mechanical jaundice, non-malignant
  • 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 the age of 18 (incl.).
  3. Obstructive jaundice, verified by enlargement of intrahepatic bile ducts with proven non-tumor obstruction of extrahepatic bile ducts.
  4. Duration of mechanical jaundice 15 days or less.
  5. The level of total bilirubin in the blood from 5-fold to 20-fold exceeding normal.
  6. 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
  7. Negative urine test for pregnancy in women of reproductive age.
  8. Consent to use adequate methods of contraception or for complete abstinence from sexual activity for the period of the study.
  9. Consent to abstain completely from alcohol intake during the study period.

Exclusion criteria

Exclusion Criteria:

  1. Tumor causing the obstruction of the bile ducts or the presence of any other malignancy at the time of randomization.
  2. The need for another radical surgery within 2 weeks from the planned date of randomization.
  3. Acute destructive pancreatitis, diffuse or diffuse peritonitis, sepsis.
  4. Preexisting liver cirrhosis.
  5. Exacerbation of the chronic peptic ulcer.
  6. Ongoing bleeding.
  7. 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.
  8. Any other decompensated disease.
  9. Pregnancy or lactation.
  10. Hypersensitivity to any component of the study drug / placebo and / or intolerance to any component of the study drug / placebo.
  11. Regular admission of medications prohibited or not permitted by the study protocol within 4 weeks prior to enrollment.
  12. Concomitant chronic systemic immune or hormonal therapy.
  13. Gout.
  14. Alcohol and/or drug dependence.
  15. Active tuberculosis, HIV infection, syphilis, acute viral hepatitis.
  16. Any other conditions / diseases that may interfere with the patient's compliance with the requirements of the Protocol.
  17. Mental, physical and other reasons that do not allow the patient to comply with the requirements of the study protocol.
  18. Any other significant (by judgement of the investigator) condition that prevents the patient from entering the study.
  19. Participation in any clinical trial in the previous 3 months.
  20. 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
342 participants (actual)

Study arms

  • Experimental
    Remaxol 400 ml

    Group I: treatment with Remaxol 400 ml IV + Ringer solution 400 ml IV for 7 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)

    Drug: Remaxol (succinate + methionine + inosine + nicotinamide) · Drug: Ringer's Solution

  • Experimental
    Remaxol 800 ml

    Group II: treatment with Remaxol 800 ml IV for 7 days. Drug: Remaxol (succinate + methionine + inosine + nicotinamide)

    Drug: Remaxol (succinate + methionine + inosine + nicotinamide)

  • Placebo comparator
    Control

    Group III: Ringer's solution 800 ml IV for 7 days. Drug: Ringer's solution

    Drug: Ringer's Solution

Interventions

  • DrugRemaxol (succinate + methionine + inosine + nicotinamide)

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

    Also known as: Remaxol®

  • DrugRinger's Solution

    Intravenous infusion, 400 or 800 ml

    Also known as: Placebo

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: 14 days

Secondary outcomes

  1. 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

    Time frame: 5 days

  2. 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

    Time frame: 5 days

  3. 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

    Time frame: 5 days

  4. Serum bilirubin

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

    Time frame: 14 days

  5. Serum enzymes

    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

  6. 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

    Time frame: 14 days

  7. Kidney function

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

    Time frame: 14 days

  8. 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: 14 days

06

Study locations

13 sites
  • Moscow 'City Clinical Hospital #24
    Moscow, 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
  • Moscow City Clinical Hospital #67 n.a. L.A.Vorohobova
    Moscow, Russian Federation
  • Novosibirsk State Medical University
    Novosibirsk, Russian Federation
  • City Clinical Hospital of Emergency Care
    Ryazan, Russian Federation
  • North-West State Medical University named after I.I. Mechnikov
    Saint Petersburg, 191015, Russian Federation
  • State Budgetary Health Care Institution "City Hospital № 26"
    Saint Petersburg, 196247, Russian Federation
  • Hospital for War Veterans
    Saint Petersburg, Russian Federation
  • Leningrad Regional Clinical Hospital
    Saint Petersburg, Russian Federation
  • Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
    Saint Petersburg, Russian Federation
  • City Clinical Hospital #3 n.a.B.I.Alperovich
    Tomsk, Russian Federation
  • GBUZ YO 'Regional Clinical Hospital'
    Yaroslavl, 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
NCT03418935
Lead sponsor
POLYSAN Scientific & Technological Pharmaceutical Company
Responsible party
Sponsor
First posted
Feb 1, 2018
Start date
Apr 3, 2017
Primary completion
Mar 31, 2020
Completion
Apr 13, 2020
Last update
Jul 14, 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
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