Clinical trial NCT03418935: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Jaundice, Obstructive
Keywords: obstructive jaundice, non-malignant
mechanical jaundice, non-malignant
Methionine
Succinic acid
Lead sponsor: POLYSAN Scientific & Technological Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2018-02-01
Enrollment: 342
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 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.

Eligibility criteria: 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:

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.

Primary outcomes:
measure: Days to regression of jaundice
timeFrame: 14 days
Secondary outcomes:
measure: Disappearance of cytolysis (normal alanine aminotransferase and aspartate aminotransferase serum levels) on day 5
timeFrame: 5 days
measure: Disappearance of cholestasis on day 5
timeFrame: 5 days
measure: Disappearance of encephalopathy on day 5
timeFrame: 5 days
measure: Serum bilirubin
timeFrame: 14 days
measure: Serum enzymes
timeFrame: 14 days
measure: Liver function
timeFrame: 14 days
measure: Kidney function
timeFrame: 14 days
measure: Proportion of patients with complications of jaundice
timeFrame: 14 days
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Moscow 'City Clinical Hospital #24
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: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital #67 n.a. L.A.Vorohobova
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk State Medical University
city: Ryazan
country: Russian Federation
facility: City Clinical Hospital of Emergency Care
city: Saint Petersburg
country: Russian Federation
facility: North-West State Medical University named after I.I. Mechnikov
city: Saint Petersburg
country: Russian Federation
facility: State Budgetary Health Care Institution "City Hospital № 26"
city: Saint Petersburg
country: Russian Federation
facility: Hospital for War Veterans
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg I.I.Dzanelidze Research Institute of Emergency Medicine
city: Tomsk
country: Russian Federation
facility: City Clinical Hospital #3 n.a.B.I.Alperovich
city: Yaroslavl
country: Russian Federation
facility: GBUZ YO 'Regional Clinical Hospital'
Study officials:
affiliation: St. Petersburg State Medical University n.a. I.P.Pavlov.
name: Mikhail S. Bogomolov, MD, PhD
role: STUDY_DIRECTOR
References: