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Pilot Study of Reparixin for Early Allograft Dysfunction Prevention in Liver Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03031470
Recruitment Status : Completed
First Posted : January 25, 2017
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A

Brief Summary:

Liver transplantation is currently the treatment of choice for end-stage liver cirrhosis of different origin, as well as for a number of inborn metabolism disorders and liver tumors. The need to perform a liver transplantation is high and amounts to 10 - 20 patients per 1 million population per year.

Experimental and clinical evidence demonstrate the harmful short and long-term effects of ischemia-reperfusion injury (IRI) of the donor organ on the outcome of the intervention performed. Severe manifestations of IRI of the liver transplant (LT) is one of the main reasons for the increased length of hospitalization, the high cost of treating patients during the post- surgery period, the development of persistent early allograft dysfunction or loss, frequent crises of acute rejection, acute renal and multiple organ failure, and mortality of the operated patients.

This pilot clinical study is designed to evaluate the efficacy and safety of Reparixin, which is a new, potent and specific inhibitor of chemokine CXCL8 (Interleukin-8), as an agent to prevent early allograft dysfunction caused by ischemia-reperfusion injury in patients undergoing orthotopic liver transplantation.


Condition or disease Intervention/treatment Phase
Ischemia-reperfusion Injury in Liver Transplant Early Allograft Dysfunction Drug: Reparixin Other: Standard care procedures Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 2015
Actual Primary Completion Date : February 9, 2017
Actual Study Completion Date : March 31, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Reparixin
Reparixin 2.772 mg/kg/hour 168 hrs continuous intravenous infusion
Drug: Reparixin
Reparixin 168 hrs continuous infusion

Standard Care Procedures
No treatment; standard care procedure
Other: Standard care procedures
Standard procedures for administration of Immunosuppressive and support post transplant therapies




Primary Outcome Measures :
  1. % Early Allograft Dysfunction [ Time Frame: Week 1 ]
    % Early Allograft Dysfunction after Week 1 post transplant


Secondary Outcome Measures :
  1. Primary nonfuntion [ Time Frame: Day 7 ]
    Primary nonfunction within 7 days after OLT defined by liver function tests

  2. Overall dysfunction [ Time Frame: Day 14 ]

    Overall indication of liver allograft disfunction, including:

    I) primary nonfuntion II) early allograft dysfunction defined as maximum alanine transferase (ALT) or aspartate transferase (AST) levels on days 1-7 of >2000 U/ml, day 7 bilirubin level ≥10 mg/dl, or a day 7 international normalized ratio (INR) ≥1.7, III) extracorporeal detoxification


  3. Time to Liver Function normalization [ Time Frame: Month 12 ]
    Time for normalization of liver function parameters after OLT

  4. Mortality at month 12 [ Time Frame: Month 12 ]
    Mortality within 1 year after OLT

  5. Graft survival month 12 [ Time Frame: Month 12 ]
    Graft survival at 1 year after OLT

  6. AE [ Time Frame: Month 12 ]
    Adverse events during 1 years after OLT

  7. Incidence of extracorporeal detoxification [ Time Frame: Month 12 ]
    The incidence of severe allograft dysfunction, which required extracorporeal detoxification

  8. ALT [ Time Frame: Month 12 ]
    Change from baseline value

  9. AST [ Time Frame: Month 12 ]
    Change from baseline

  10. GGT [ Time Frame: Month 12 ]
    Change from baseline

  11. Total Bilirubin [ Time Frame: Month 12 ]
    Change from baseline



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03031470


Locations
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Belarus
Healthcare Organization "9th City Clinical Hospital"
Minsk, Belarus, 220045
Russian Federation
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
Krasnodar, Krasnodar Territory, Russian Federation, 350086
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
St. Petersburg, Saint Petersburg, Russian Federation, 197022
Federal State Budgetary Institution "Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs" Ministry of Health of the Russian Federation
Moscow, Russian Federation, 123182
Federal State Budgetary Institution "State Research Centre of the Russian Federation - Federal Medical Biophysical Centre n.a. A.I. Burnazyan"
Moscow, Russian Federation, 123182
State Budgetary Health Institution of Moscow "Scientific Research Institute of Emergency n.a. N.V. Sklifosovskiy of Moscow Healthcare Department"
Moscow, Russian Federation, 129090
State Budgetary Health Institution of Novosibirsk Region "State Novosibirsk Regional Clinical Hospital"
Novosibirsk, Russian Federation, 630087
Sponsors and Collaborators
Dompé Farmaceutici S.p.A
Investigators
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Principal Investigator: Sergey Vladimirovich Zhuravel, MD State Budgetary Health Institution of Moscow "Scientific Research Institute of Emergency n.a. N.V. Sklifosovskiy of Moscow Healthcare Department"
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Responsible Party: Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier: NCT03031470    
Other Study ID Numbers: TPL-RPX-01
First Posted: January 25, 2017    Key Record Dates
Last Update Posted: July 24, 2018
Last Verified: July 2018
Keywords provided by Dompé Farmaceutici S.p.A:
Liver Transplant
Ischemia-reperfusion injury
Early allograft dysfunction
Additional relevant MeSH terms:
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Reperfusion Injury
Ischemia
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications