Clinical trial NCT03416062: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Jaundice; Malignant
Keywords: Jaundice, obstructive
Methionine
Succinic acid
Lead sponsor: POLYSAN Scientific & Technological Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2018-01-30
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to regression of jaundice
timeFrame: 21 days
Secondary outcomes:
measure: Regression of cytolysis (normal alanine aminotransferase and aspartate aminotransferase serum levels)
timeFrame: 11 days
measure: Regression of cholestasis
timeFrame: 11 days
measure: Regression of encephalopathy
timeFrame: 11 days
measure: Serum bilirubin
timeFrame: 21 days
measure: Serum alkaline phosphatase
timeFrame: 21 days
measure: Serum GGTP
timeFrame: 21 days
measure: Serum alanine aminotransferase
timeFrame: 21 days
measure: Serum aspartate aminotransferase
timeFrame: 21 days
measure: Liver function
timeFrame: 21 days
measure: Kidney function
timeFrame: 21 days
measure: Proportion of patients with complications of jaundice
timeFrame: 21 days
measure: Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: 31 days
Other outcomes:
Locations:
city: Bryansk
country: Russian Federation
facility: GBUZ 'Bryansk City Hospital #1'
city: Kemerovo
country: Russian Federation
facility: Regional Clinical Hospital of Emergency Care n.a.M.A.Podgorbunsky
city: Krasnoyarsk
country: Russian Federation
facility: KBUZ 'Regional Clinical Hospital'
city: Kursk
country: Russian Federation
facility: OBUZ 'Kursy Regional Clinical Oncology Dispensary' of Kursky Regional Healthcare Department
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital #1 n.a.N.I.Pirogov
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital #29 n.a.N.A.Bauman
city: Omsk
country: Russian Federation
facility: Omsk Regional Clinical Oncology Center
city: Penza
country: Russian Federation
facility: GBUZ "Penza Regional Clinical Hospital na N.N.Burdenko"
city: Ryazan
country: Russian Federation
facility: City Clinical Hospital of Emergency Care
city: Saint Petersburg
country: Russian Federation
facility: GBUZ 'Leningrad Regional Oncology Center'
city: Saint Petersburg
country: Russian Federation
facility: GBUZ Leningrad Regional Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: Hospital for War Veterans
city: Saint Petersburg
country: Russian Federation
facility: North-West State Medical University named after I.I. Mechnikov
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
city: Saint Petersburg
country: Russian Federation
facility: SPb GBUZ "City Hospital №26"
city: Saint Petersburg
country: Russian Federation
facility: SPb GBUZ 'City Mariinskaya Hospital'
city: Tomsk
country: Russian Federation
facility: OGAUZ "Tomsk Regional Clinical Hospital"
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
Study officials:
affiliation: St. Petersburg State Medical University n.a. I.P.Pavlov
name: Mikhail S. Bogomolov, MD, PhD
role: STUDY_DIRECTOR
References: