search
Back to results

Effect Of DAAs For Treatment Of HCV On Normal Kidney

Primary Purpose

Antiviral Drug Adverse Reaction

Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Sofosbuvir 400 MG Oral Tablet,
Ombitasvir/paritaprevir/ritonavir
Sponsored by
Assiut University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Antiviral Drug Adverse Reaction focused on measuring Direct Acting Antiviral Agents (DAAs)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Both male and female patients with age above 18 years presented with chronic HCV infection (diagnosed by HCV RNA positive) with normal kidney functions, i.e.:

    • Normal S.creatinine
    • Normal urine analysis (without proteinuria, haematuria or abnormal casts).
    • Normal renal sonography.
  • and candidate for direct acting antiviral drugs.

Exclusion Criteria:

  • Any chronic HCV patient with known renal disease.
  • Patients with abnormal kidney functions, i.e.:

    • Abnormal S.creatinine.
    • Abnormal urine analysis (with proteinuria, haematuria or abnormal casts).
    • Abnormal renal US
  • Any other known renal disease (lupus nephritis, diabetic nephropathy).
  • Severe co-morbidity as severe heart failure or malignancy.
  • Other liver disease (autoimmune hepatitis, HBV, Wilson, ……).
  • Decompansated liver disease (ascites, hepatic encephalopathy, …).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Active Comparator

    Arm Label

    first drug group

    second drug group

    Arm Description

    Sofosbuvir 400 MG Oral Tablet

    Ombitasvir/paritaprevir/ritonavir

    Outcomes

    Primary Outcome Measures

    Effect of the direct acting antiviral agents used for HCV treatment on the function of the normal kidney by measurement of serum creatinine.
    assessment of the renal toxicity of direct acting antivirals used for HCV treatment by measurement of the serum creatinine to detect any deviation beyond the normal values.

    Secondary Outcome Measures

    Full Information

    First Posted
    September 16, 2017
    Last Updated
    September 26, 2017
    Sponsor
    Assiut University
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03296930
    Brief Title
    Effect Of DAAs For Treatment Of HCV On Normal Kidney
    Official Title
    Effect Of Interferon-Free Direct Acting Antiviral Agents For Treatment Of Hepatitis C Virus Patients On The Normal Kidney
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2017
    Overall Recruitment Status
    Unknown status
    Study Start Date
    October 1, 2017 (Anticipated)
    Primary Completion Date
    September 30, 2018 (Anticipated)
    Study Completion Date
    October 31, 2018 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Assiut University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    The aim of the study is to determine the effect of different direct acting antiviral drugs used for treatment of chronic HCV infected patients on normal kidney.
    Detailed Description
    Hepatitis C virus (HCV) infection is a major health problem. The World Health Organization (WHO) estimated that at least 150-170 million people, approximately 3% of the world's population, are chronically infected. These patients are known to be at risk of developing liver complications, i.e., cirrhosis and liver cancer, with an estimated liver-related mortality of 350,000 people/year. However, the risks of morbidity and mortality are underestimated because they do not take into account the extra-hepatic consequences of HCV infection. Numerous extra-hepatic manifestations (HCV-EHMs) have been reported. In some large cohort studies, up to 74% of patients experienced HCV-EHMs of different severity, from perceived to disabling conditions. Treatment of HCV infection has a long history. It began with interferon (IFN) mono-therapy, with less than 20% sustained virological response (SVR). Milestones include the addition of ribavirin (RBV) to the treatment protocol and providing pegylated-IFN (PegIFN) as an alternative treatment. Treatment with PegIFN/RBV was the standard of care for about 10 years. The success rate of treatment with this regimen is very dependent on patient characteristics, including age, body mass index, ethnicity, and genetic factors. Viral factors, especially HCV genotype, also affect the response to HCV treatment, and there are always additional factors that should be taken into account in each treatment approach, including treatment success rate, duration, cost, and side effects. In light of these concerns, attempts have continued to introduce better therapeutic regimens. Treatment of chronic HCV infection has been revolutionized in recent years. The FDA has approved different IFN-free direct acting antiviral regimens (DAAs) including: Sofosbuvir (SOF) in combination with Ledipasvir (LDV), combination of Ombitasvir/Paritaprevir/ Dasabuvir (a three direct acting antiviral, or 3D), combination therapy with Grazoprevir/Elbasvir (GZR/EBR), Simeprevir (SMV) and Daclatasvir (DCV) also in combination with SOF. More than 95% of patients have a sustained viral response (SVR) using DAA. The recent Cohort studies have demonstrated that the new regimens of DAAs may be associated with renal side effects, especially when using SOF combinations. So, to aid in the correct use of DAAs in treatment of HCV patients, their potential renal toxicity must be known. The close monitoring of renal function is required. Although, new DAAs were well tolerated, recent real-life studies have demonstrated some nephrotoxic effect in Frail populations treated with SOF based regimens. The use of direct acting antiviral agents (DAAs) in HCV patients might be expected to result in improved outcomes in hepatic functions even in end stage liver disease. But, the effect of DAAs on the kidney still needing a specific study.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Antiviral Drug Adverse Reaction
    Keywords
    Direct Acting Antiviral Agents (DAAs)

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Non-Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    first drug group
    Arm Type
    Active Comparator
    Arm Description
    Sofosbuvir 400 MG Oral Tablet
    Arm Title
    second drug group
    Arm Type
    Active Comparator
    Arm Description
    Ombitasvir/paritaprevir/ritonavir
    Intervention Type
    Drug
    Intervention Name(s)
    Sofosbuvir 400 MG Oral Tablet,
    Other Intervention Name(s)
    daclatasvir, ribavirin
    Intervention Description
    Interferon free direct acting antiviral drugs used for treatment of HCV.
    Intervention Type
    Drug
    Intervention Name(s)
    Ombitasvir/paritaprevir/ritonavir
    Other Intervention Name(s)
    ribavirin
    Intervention Description
    Interferon free direct acting antiviral drugs used for treatment of HCV.
    Primary Outcome Measure Information:
    Title
    Effect of the direct acting antiviral agents used for HCV treatment on the function of the normal kidney by measurement of serum creatinine.
    Description
    assessment of the renal toxicity of direct acting antivirals used for HCV treatment by measurement of the serum creatinine to detect any deviation beyond the normal values.
    Time Frame
    one year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Both male and female patients with age above 18 years presented with chronic HCV infection (diagnosed by HCV RNA positive) with normal kidney functions, i.e.: Normal S.creatinine Normal urine analysis (without proteinuria, haematuria or abnormal casts). Normal renal sonography. and candidate for direct acting antiviral drugs. Exclusion Criteria: Any chronic HCV patient with known renal disease. Patients with abnormal kidney functions, i.e.: Abnormal S.creatinine. Abnormal urine analysis (with proteinuria, haematuria or abnormal casts). Abnormal renal US Any other known renal disease (lupus nephritis, diabetic nephropathy). Severe co-morbidity as severe heart failure or malignancy. Other liver disease (autoimmune hepatitis, HBV, Wilson, ……). Decompansated liver disease (ascites, hepatic encephalopathy, …).
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hazem Y Shouman, M.B.B.Ch
    Phone
    +201111114746
    Email
    dr.hazem.shoman1@gmail.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Zainelabdeen A Sayed, MD
    Organizational Affiliation
    Assistant Professor of Internal Medicine
    Official's Role
    Study Chair
    First Name & Middle Initial & Last Name & Degree
    Mohammed M Abdallah, MD
    Organizational Affiliation
    Professor of Internal Medicine
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    27110259
    Citation
    Behnava B, Sharafi H, Keshvari M, Pouryasin A, Mehrnoush L, Salimi S, Karimi Elizee P, Ghazimoghaddam M, Alavian SM. The Role of Polymorphisms Near the IL28B Gene on Response to Peg-Interferon and Ribavirin in Thalassemic Patients With Hepatitis C. Hepat Mon. 2016 Jan 23;16(1):e32703. doi: 10.5812/hepatmon.32703. eCollection 2016 Jan.
    Results Reference
    background
    PubMed Identifier
    25458776
    Citation
    Cacoub P, Gragnani L, Comarmond C, Zignego AL. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis. 2014 Dec 15;46 Suppl 5:S165-73. doi: 10.1016/j.dld.2014.10.005. Epub 2014 Nov 8.
    Results Reference
    background
    PubMed Identifier
    27917261
    Citation
    Carrier P, Essig M, Debette-Gratien M, Sautereau D, Rousseau A, Marquet P, Jacques J, Loustaud-Ratti V. Anti-hepatitis C virus drugs and kidney. World J Hepatol. 2016 Nov 18;8(32):1343-1353. doi: 10.4254/wjh.v8.i32.1343.
    Results Reference
    background
    PubMed Identifier
    25911336
    Citation
    European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol. 2015 Jul;63(1):199-236. doi: 10.1016/j.jhep.2015.03.025. Epub 2015 Apr 21. No abstract available.
    Results Reference
    background
    PubMed Identifier
    24795200
    Citation
    Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, Cooper C, Tam E, Marinho RT, Tsai N, Nyberg A, Box TD, Younes Z, Enayati P, Green S, Baruch Y, Bhandari BR, Caruntu FA, Sepe T, Chulanov V, Janczewska E, Rizzardini G, Gervain J, Planas R, Moreno C, Hassanein T, Xie W, King M, Podsadecki T, Reddy KR; PEARL-III Study; PEARL-IV Study. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014 May 22;370(21):1983-92. doi: 10.1056/NEJMoa1402338. Epub 2014 May 4.
    Results Reference
    background
    PubMed Identifier
    26269684
    Citation
    Haj-Sheykholeslami A, Keshvari M, Sharafi H, Pouryasin A, Hemmati K, Mohammadzadehparjikolaei F. Interferon-lambda polymorphisms and response to pegylated interferon in Iranian hepatitis C patients. World J Gastroenterol. 2015 Aug 7;21(29):8935-42. doi: 10.3748/wjg.v21.i29.8935.
    Results Reference
    background
    PubMed Identifier
    26799692
    Citation
    Kwo P, Gitlin N, Nahass R, Bernstein D, Etzkorn K, Rojter S, Schiff E, Davis M, Ruane P, Younes Z, Kalmeijer R, Sinha R, Peeters M, Lenz O, Fevery B, De La Rosa G, Scott J, Witek J. Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study. Hepatology. 2016 Aug;64(2):370-80. doi: 10.1002/hep.28467. Epub 2016 Mar 22.
    Results Reference
    background
    PubMed Identifier
    16422999
    Citation
    Lee SS, Bain VG, Peltekian K, Krajden M, Yoshida EM, Deschenes M, Heathcote J, Bailey RJ, Simonyi S, Sherman M; CANADIAN PEGASYS STUDY GROUP. Treating chronic hepatitis C with pegylated interferon alfa-2a (40 KD) and ribavirin in clinical practice. Aliment Pharmacol Ther. 2006 Feb 1;23(3):397-408. doi: 10.1111/j.1365-2036.2006.02748.x. Erratum In: Aliment Pharmacol Ther. 2006 Apr 1;23(7):1029.
    Results Reference
    background
    PubMed Identifier
    11583749
    Citation
    Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65. doi: 10.1016/s0140-6736(01)06102-5.
    Results Reference
    background
    PubMed Identifier
    24631495
    Citation
    Pawlotsky JM. New hepatitis C therapies: the toolbox, strategies, and challenges. Gastroenterology. 2014 May;146(5):1176-92. doi: 10.1053/j.gastro.2014.03.003. Epub 2014 Mar 12.
    Results Reference
    background
    PubMed Identifier
    22368678
    Citation
    Sharafi H, Alavian SM. IL28B polymorphism, Explanation for Different Responses to Therapy in Hepatitis C Patients. Hepat Mon. 2011 Dec;11(12):958-9. doi: 10.5812/kowsar.1735143X.794. Epub 2011 Dec 20. No abstract available.
    Results Reference
    background
    PubMed Identifier
    24428467
    Citation
    Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds W, Pasquinelli C, Grasela DM; AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218. Erratum In: N Engl J Med. 2014 Apr 10;370(15):1469.
    Results Reference
    background
    PubMed Identifier
    9303508
    Citation
    Tong MJ, Reddy KR, Lee WM, Pockros PJ, Hoefs JC, Keeffe EB, Hollinger FB, Hathcote EJ, White H, Foust RT, Jensen DM, Krawitt EL, Fromm H, Black M, Blatt LM, Klein M, Lubina J. Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group. Hepatology. 1997 Sep;26(3):747-54. doi: 10.1002/hep.510260330.
    Results Reference
    background
    PubMed Identifier
    25909356
    Citation
    Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z, Zhao Y, Brown DD, Wan S, DiNubile MJ, Nguyen BY, Robertson MN, Wahl J, Barr E, Butterton JR. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med. 2015 Jul 7;163(1):1-13. doi: 10.7326/M15-0785.
    Results Reference
    background

    Learn more about this trial

    Effect Of DAAs For Treatment Of HCV On Normal Kidney

    We'll reach out to this number within 24 hrs