Clinical trial NCT03031470: Pilot Study of Reparixin for Early Allograft Dysfunction Prevention in Liver Transplantation
Official title: A Multicenter, Open-label, Randomized Pilot Clinical Study of Efficacy and Safety of Reparixin for Prevention of Early Allograft Dysfunction in Patients Undergoing Orthotopic Liver Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ischemia-reperfusion Injury in Liver Transplant
Early Allograft Dysfunction
Keywords: Liver Transplant
Ischemia-reperfusion injury
Early allograft dysfunction
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2017-01-25
Enrollment: 40
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 objective of the study is to evaluate the efficacy and safety of Reparixin treatment (2.772 mg/kg body weight/hour intravenous continuous infusion for 7 days) based on incidence of early allograft dysfunction within the first 7 days after orthotopic liver transplantation (OLT) and overall indicators of allograft dysfunction in the early postoperative period (within 14 days after the OLT).

Detailed description: The study is a phase 2, multicenter, open-label, randomized pilot study to evaluate the efficacy and safety of Reparixin for prevention of early allograft dysfunction in patients undergoing orthotopic liver transplantation.

All the patients who participated in the study received standard immunosuppressive therapy in accordance with the Russian Transplant Society Guidelines for liver transplantation (2013). The study was planned to be conducted at 5-8 transplantation sites in Russia and Belarus. Recruitment was competitive among the study sites so that patients were screened and if eligible, randomized consecutively until the randomization was stopped.

Eligibility criteria: Inclusion Criteria:

1. Male and female patients aged 18 years and older needing a whole organ OLT, listed on the waiting list for liver transplantation.
2. Severity score of the initial condition of the patient (hepatocellular dysfunction) according to the scales of Child-Turcotte-Pugh ≥ 7 points or MELD 15-40 points (or both).
3. The possibility of insertion of a central catheter for infusion of the study drug.
4. Signed Patient Informed Consent Form.
5. Ability to comply with all the requirements of the protocol.
6. Consent to use adequate contraception means throughout the study. The adequate contraception methods include use of condom with spermicide.

Exclusion Criteria:

Patients with any of the following conditions shall not be included in the study:

1. Split-liver transplantation or transplantation from a living donor.
2. Re-transplantation or multivisceral transplantation.
3. The presence of extrahepatic tumor foci or sepsis.
4. Gastrointestinal bleeding caused by portal hypertension within 3 months prior to screening.
5. BMI less than 18.5 or more than 40 kg/m2.
6. HIV infection.
7. Significant cardiovascular disease at the present time or within 6 months prior to screening, including: class III or IV chronic heart failure (the New York Heart Association), myocardial infarction, unstable angina, hemodynamically significant cardiac arrhythmias, ischemic or hemorrhagic stroke, uncontrolled arterial hypertension.
8. Preoperative renal impairment (glomerular filtration rate estimated with the Cockcroft-Gault formula ≤ 45 mL/min).
9. Significant, in the opinion of the Investigator, drug or alcohol abuse within 6 months prior to screening.
10. Hypersensitivity to:

    1. ibuprofen or to more than one non-steroidal anti-inflammatory drug (NSAID),
    2. more than one medication belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib; hypersensitivity to sulphanilamide antibiotics alone (e.g. sulfamethoxazole) does not qualify for exclusion.
11. Pregnant or lactating women, or women planning a pregnancy during the clinical study, fertile women not using adequate contraception methods.
12. Participation in another clinical study currently or within 30 days prior to screening, use of any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to screening.
13. The patient's and his/her relatives' failure to understand the need for lifelong immunosuppressive therapy, as well as the risk and difficulty of the pending operation and the subsequent dynamic treatment.
14. Inability to read or write; unwillingness to understand and comply with the procedures of the study protocol; failure to comply with the treatment, which, in opinion of the Investigator, may affect the results of the study or the patient's safety and prevent the patient from further participation in the study; any other associated medical or serious mental conditions that make the patient unsuitable for participation in the clinical study, limit the validity of informed consent or may affect the patient's ability to participate in the study.

Primary outcomes:
measure: Incidence of EAD (Early Allograft Dysfunction) Within 7 Days After OLT (PP Population)
timeFrame: within 7 day after the OLT
measure: Incidence of EAD (Early Allograft Dysfunction) Within 7 Days After OLT (mITT Population)
timeFrame: within 7 day after the OLT
Secondary outcomes:
measure: Number of Patients With/Without Primary Allograft Nonfunction Within 7 Days After OLT
timeFrame: Within 7 days after OLT
measure: Number of Patients With/Without Overall Indicators of Allograft Dysfunction During the Early Postoperative Period
timeFrame: Within 14 days after OLT
measure: Overall Indicators of the Allograft Dysfunction During the Early Postoperative Period - Extracorporeal Detoxification
timeFrame: Within 14 days after OLT
measure: Frequency of Identification of Laboratory Examination Values
timeFrame: within 3 day after the OLT
measure: Number of Patients With Early Allograft Dysfunction (EAD) in Case of Transplantation of Donor Organs, by the Degree of Steatosis
timeFrame: Within 14 days after OLT
measure: Number of Patients With EAD in Case of Transplantation of Donor Organs Differing by the Time (in Hours) of Allograft Removal From the Donor and up to Its Reperfusion (Duration of Cold Ischemia)
timeFrame: Within 14 days after OLT
measure: Number of Patients With EAD in Case of Transplantation of Donor Organs Differing by the Duration (in Min) of Warm Ischemia
timeFrame: Within 14 days after OLT
measure: Number of Patients With EAD in Transplantation From Donors Having Additional Adverse Factors
timeFrame: Within 14 days after OLT
measure: Number of Patients With EAD in Transplantation With Regard to the Interval (in Hours) Between the Diagnosis of Brain Death and Removal of the Liver Graft From a Donor
timeFrame: Within 14 days after OLT
measure: Number of Patients With EAD in Transplant Recipients With Each of the Different Liver Disease Etiology
timeFrame: Within 14 days after OLT
measure: Incidence of Early Allograft Dysfunction (EAD) in Transplant Recipients With Liver Diseases of Different Etiology and With Different Baseline Characteristics
timeFrame: Within 14 days after OLT
measure: The Number of Patients With EAD in Transplant Recipients With Liver Diseases (HBV and HCV Virus) and With Different Baseline Characteristics
timeFrame: Within 14 days after OLT
measure: Incidence of Early Allograft Dysfunction in Transplant Recipients (Creatinine Clearance, ClCr)
timeFrame: Within 14 days after OLT
measure: Incidence of Early Allograft Dysfunction in Transplant Recipients - Severity of Recipient's Liver Disease Through MELD Index
timeFrame: Within 14 days after OLT
measure: Number of Patients With EAD in Transplant Recipients Via Child-Turcotte-Pugh Score (CTP)
timeFrame: Within 14 days after OLT
measure: Time to Liver Function Normalization of Liver Function Parameters
timeFrame: Within 1 Year after OLT
measure: Patient Survival Within 1 Year After OLT
timeFrame: within 1 year after OLT
measure: Mortality Within 1 Year After the OLT
timeFrame: Within 1 Year after OLT
measure: The Incidence of Hyperacute, Acute and Chronic Liver Allograft Rejection .
timeFrame: Within 1 Year after OLT
measure: Summary of Adverse Events up to 1 Year After the OLT
timeFrame: up to 1 year after the OLT
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: Healthcare Organization "9th City Clinical Hospital"
city: Krasnodar
country: Russian Federation
facility: State Budgetary Health Institution "Scientific Research Institute - Regional Clinical Hospital # 1 n.a. professor S.V. Ochapovskiy" of the Ministry of Health of the Krasnodar Territory
state: Krasnodar Territory
city: St. Petersburg
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "First Saint Petersburg State Medical University n.a. I.P. Pavlov" of the Ministry of Health of the Russian Federation
state: Saint Petersburg
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs" Ministry of Health of the Russian Federation
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "State Research Centre of the Russian Federation - Federal Medical Biophysical Centre n.a. A.I. Burnazyan"
city: Moscow
country: Russian Federation
facility: State Budgetary Health Institution of Moscow "Scientific Research Institute of Emergency n.a. N.V. Sklifosovskiy of Moscow Healthcare Department"
city: Novosibirsk
country: Russian Federation
facility: State Budgetary Health Institution of Novosibirsk Region "State Novosibirsk Regional Clinical Hospital"
Study officials:
affiliation: Moscow Scientific Research Institute of Emergency, NV Sklifosovskiy of Moscow Healthcare Department
name: Sergey Vladimirovich Zhuravel, MD
role: PRINCIPAL_INVESTIGATOR
References: