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
About this trial
This is an interventional treatment trial for Antiviral Drug Adverse Reaction focused on measuring Direct Acting Antiviral Agents (DAAs)
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, …).
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
NCT ID
NCT03296930
First Posted
September 16, 2017
Last Updated
September 26, 2017
Sponsor
Assiut University
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