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Trial About Hepatic Security of Antiretroviral Treatment Based on Kaletra Versus Nevirapine in co-Infected HIV/HCV Patients

This study has been terminated.
(It has been impossible to achieve the number of patients defined by protocol)
Sponsor:
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00661349
First received: April 10, 2008
Last updated: April 22, 2009
Last verified: April 2009
  Purpose

In retrospective studies, acceleration of hepatic fibrosis has been seen in Nevirapine (NVP) treatment when compared with Protease Inhibitors (PI) boosted with ritonavir treatment in patients with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) infection. The high incidence in our country of HIV-HCV co-infection, the availability of a new Kaletra (LPV/r) formulation (more convenient and better tolerated than soft capsules) as well as the possibility of analyzing hepatic fibrosis evolution in a fast and bloodless way, make attractive a study that, in a prospective way, could check the benefits of substituting NVP by LPV/r on hepatic fibrosis in this community.


Condition Intervention Phase
HIV Infections
Drug: Lopinavir/ritonavir
Drug: Nevirapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective, Open Label and Randomized Clinical Trial About Hepatic Security of Antiretroviral Treatment Based on Kaletra Versus Nevirapine in co-Infected HIV/HCV Patients

Resource links provided by NLM:


Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • The average of hepatic rigidity increase in each group. Hepatic rigidity will be measured in kilopascals through elastography (Fibroscan). Distribution of hepatic rigidity will be normalized by a logarithmic transformat [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Virological and immunologic efficacy will be assessed through the proportion of patients with virological failure during the follow-up and the CD4 lymphocytes count of both treatment regimens. [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: No ]
  • The effect of both treatments in lipidic and glucidic metabolism will be assessed through the following variables: Total Cholesterol, HDL and LDL Cholesterol, Triglycerides and Glucose. [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
  • Higher than log 7.2 Kpa in patients with non-significant basal fibrosis (less than log 7.2 Kpa) [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
  • The security of each regimen will be studied through the proportion of patients who give up treatment because of adverse events and hepatic-related adverse events presence. [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
  • Toxicity will be determined depending on: Clinical History and Physical Examination; Coagulation, hemogram and chemistry tests, which will include: transaminase levels, GGT, alkaline phosphatase, bilirrubin, albumin, urea and creatinin [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
  • Mortality rate during the study will be evaluated. [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: February 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Nevirapine
Drug: Nevirapine
2 ITIAN (o 1 ITIAN+TDF)+ nevirapine, 2 tablet 200/50 mg to 12 hours
Experimental: 2
Lopinavir/ritonavir
Drug: Lopinavir/ritonavir
2 ITIAN (o 1 ITIAN+TDF)+ lopinavir/ritonavir, 2 tablet 200/50 mg to 12 hours

Detailed Description:

The prevalence of the HIV-HCV co-infection in Spain is one of the highest because both infections are strongly related to parenteral drugs use; so, from 61 to 69 % of HIV infected patients are also HCV infected.

Acute HCV infection is asymptomatic in 60 to 70% of cases, being the chronification the natural illness evolution. 20% of the patients will develop hepatic cirrhosis after 20 to 30 years of being infected by the HCV. In cirrhosis cases, the hepatocellular carcinoma appears in a rate of 2 to 4% per year, according to studies done with HCV mono-infected patients. Fibrosis progression depends basically on the duration of HCV infection and on the age of infection, but also on other factors, like gender (is faster in men), alcohol consumption (worst over 50 g per day) and HIV co-infection. Several epidemiologist studies have described the negative impact of HIV co-infection, accelerating the progression to cirrhosis and the hepatocarcinoma.

The Highly Active Antiretroviral Treatment (HAART) has a positive impact on survival on co-infected patients, although the three drug families used in HAART can cause hepatic toxicity in this group of patients. Hepatic toxicity appears in 5 to 20% of patients, being more serious and common, but not exclusive, in case of NVP treatment.

On their part, not all PI have the same hepatotoxic profile. An association between serious hepatotoxicity and ritonavir at full strength, indinavir and indinavir plus saquinavir boosted with ritonavir has been found.

As far as fibrosis is concerned, there are studies that show that in HIV/HCV co-infected patients PI-based regimens are associated with a lower progression to fibrosis, while the progression rate to cirrhosis is higher in NVP-based regimens, mainly in those patients with advanced hepatic fibrosis.

Hepatic biopsy is considered the reference test to assess hepatic fibrosis, nevertheless it is an invasive, painful and with a low but potentially serious risk for the patient's life. Moreover, the viability of a hepatic biopsy can be doubted due to sampling error or interobservation variability. For that reason, several biochemist tests have been developed to reflect the hepatic fibrosis extent or stage in a reliable way. Recently a hepatic rigidity measure through elastography has been presented as a non-invasive and very promising method to assess hepatic fibrosis.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 years old or elder.
  2. HCV and HIV co-infected patients.
  3. Patients with antiretroviral treatment based in NVP plus 2 NRTIs (or 1 NRTI and Tenofovir), with undetectable viral load (under 50 copies/mL) during at least the last 24 weeks.
  4. If women and of childbearing age, negative pregnancy test. Furthermore, barrier contraceptive method must be undertaken during the study.
  5. Date and signature of the informed consent.

Exclusion Criteria:

  1. Concomitant treatment with drugs that can significantly interact with the study drugs.
  2. Opportunistic infections in the last 6 months.
  3. Patients who can be candidates for an HCV infection treatment in the next 3 years.
  4. Patients in who efficacy of previous NRTIs can not be ensured. For example, patients with mono or dual therapy history or with previous blips in whom NRTI-related mutations were identified that could reduce the sensibility to the used backbone.
  5. Active alcohol consumption (over 50 g per day) or other substance abuse.
  6. Pregnant or breastfeeding women.
  7. Patients with transaminase level over 5 times the Upper Limit of Normality (ULN) or Creatinin over 2 mg/dL or Total Bilirubin over 3 times the ULN.
  8. Any formal contraindication for being treated with the study drugs.
  9. Patients who, basing in their antiretroviral treatment history, could be considered as being infected with a virus that has no sensibility to LPV.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00661349

Locations
Spain
Hospital Son Dureta
Palma de Mallorca, Baleares, Spain, 07014
H.U. Germans Trias i Pujol - Unitat VIH, Fundació Lluita contra la Sida
Badalona, Barcelona, Spain, 08916
Hospital General Universitario de Alicante
Alicante, Spain, 03010
Hospital Clínic i Provincial de Barcelona
Barcelona, Spain, 08036
Hospital Clínico San Carlos
Madrid, Spain, 28040
Hospital Universitario la Paz
Madrid, Spain, 28046
Hospital Universitario Príncipe de Asturias
Madrid, Spain, 28005
Hospital Clínico de Salamanca
Salamanca, Spain, 37007
Hospital Universitario de Valme
Sevilla, Spain, 41014
Sponsors and Collaborators
Germans Trias i Pujol Hospital
  More Information

No publications provided

Responsible Party: LLuita Sida Foundation
ClinicalTrials.gov Identifier: NCT00661349     History of Changes
Other Study ID Numbers: A10-174 (KANELA)
Study First Received: April 10, 2008
Last Updated: April 22, 2009
Health Authority: Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:
Kaletra
Nevirapina
HCV chronic infection
Fibroscan
hepatic fibrosis
treatment experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Lopinavir
Nevirapine
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014