Lopinavir/Ritonavir Monotherapy Versus Standard Highly Active Antiretroviral Therapy (HAART) in HIV/HCV Coinfected Patients Starting Treatment With Anti-Hepatitis C Virus (HCV) Therapy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by IRCCS San Raffaele.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Abbott
Hoffmann-La Roche
Information provided by:
IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT00437684
First received: February 20, 2007
Last updated: February 5, 2009
Last verified: February 2009
  Purpose

The purpose of this study is to evaluate if the combination of Lpv/r monotherapy and anti-HCV drugs does not match with additional toxicity induced by the association of HAART and Peg-IFN + ritonavir in HIV/HCV coinfected patients.

Secondary objective is to assess if Lpv/r monotherapy during HCV-treatment is associated with HIV efficacy versus optimized HAART.


Condition Intervention Phase
HIV Infections
Hepatitis C
Drug: LPV/r
Drug: PEG-IFNa 2a
Drug: Ribavirin
Drug: NUCS
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot, Open Label, Multicenter, Randomized Clinical Trial on Lopinavir/Ritonavir-Monotherapy vs Lopinavir/Ritonavir Plus Selected Nucs, in HIV/HCV Coinfected Patients With Chronic Hepatitis C or Compensated Cirrhosis, Starting Treatment With Ribavirin and Pegylated Interferon

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • To assess if the combination of LPV/r monotherapy in association with anti-HCV [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Nucs) and PEG-IFN alfa 2a +Ribavirin in patients naïve for HCV treatment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • without previous failure or detection of any mutations related to PI resistance. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess if LPV/r monotherapy during the HCV treatment is associated with [ Time Frame: 12 and 18 months ] [ Designated as safety issue: No ]
  • anti HIV/HCV efficacy and a better patient satisfaction vs optimized HAART. [ Time Frame: 12 and 18 months ] [ Designated as safety issue: No ]
  • To assess the number and type of HIV-1 resistance mutations in patients with [ Time Frame: 12 and 18 months ] [ Designated as safety issue: No ]
  • virological failure [ Time Frame: 12 and 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2007
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
LPV/r: LPV/r monotherapy and anti HCV drugs for 12 months. All the patients will be followed-up for six months after the end of anti-HCV drugs for the evaluation of Sustained Virological Response (SVR). At the end of the co-treatment for HCV/HIV, each subject will be treated for HIV infection according to physician decisions.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day .At the end of the third month of combined therapy, only patients who reach an early virological response will continue anti-HCV drugs.
Drug: LPV/r
200/50 mg 2 cpr bid monotherapy
Drug: PEG-IFNa 2a
PEG-IFNa 2a 180 mcg/week
Drug: Ribavirin
Ribavirin 1-1.2 g/day
Active Comparator: B
LPV/r+ selected NUCS and anti HCV drugs for 12 months. All the patients will be followed-up for six months after the end of anti-HCV drugs for the evaluation of Sustained Virological Response (SVR). At the end of the co-treatment for HCV/HIV, each subject will be treated for HIV infection according to physician decisions.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day .At the end of the third month of combined therapy, only patients who reach an early virological response will continue anti-HCV drugs.
Drug: LPV/r
200/50 mg 2 cpr bid monotherapy
Drug: PEG-IFNa 2a
PEG-IFNa 2a 180 mcg/week
Drug: Ribavirin
Ribavirin 1-1.2 g/day
Drug: NUCS
Nucleoside Reverse Transcriptase Inhibitors

Detailed Description:

This is a pilot, randomised, open label, controlled clinical trial. All eligible patients(CD4>350, HIV RNA<50 copies and no PI mutations) will be randomized (1:1) to receive LPV/r new tabs (200/50 mg, 2 cpr BID) monotherapy (arm A) or LPV/r + selected NUCS (arm B) associated to anti-HCV therapy for 12 months. The number of subjects to recruit, in each arm of the study, is equal to 25, the total number of subjects to enrol will be 50.

  • Group A: will receive LPV/r monotherapy and anti HCV drugs for 12 months.
  • Group B: will receive LPV/r+ selected NUCS and anti HCV drugs for 12 months. All the patients will be followed-up for six months after the end of anti-HCV drugs for the evaluation of Sustained Virological Response (SVR). At the end of the co-treatment for HCV/HIV, each subject will be treated for HIV infection according to physician decisions.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day .At the end of the third month of combined therapy, only patients who reach an early virological response will continue anti-HCV drugs.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject is >18 years old
  • Subject has given written informed consent
  • Subject has a confirmed diagnosis of HIV and HCV infection
  • Subject is naive for HCV-infection treatment
  • Subject has chronic hepatitis and/or subject has compensated cirrhosis (Child class A)
  • Subject has a CD4+ count of > 350 cell/mmc
  • Subject is HIV-RNA negative during the previous six month
  • Subject is on stable HAART including r/LPV for > 6 months
  • Subject has genotype available at baseline and no mutations associated with resistance to PI or no virologic failure on PI treatment, defined as a confirmed HIV-RNA level>50 cp/mL after 24 weeks, > 50 cp/ml after 48 weeks, or a repeated HIV RNA level > 50 cp/mL after prior suppression of viremia to< 50 cps/mL.
  • Free of any clinically significant disease (other than HIV and HCV) that would interfere with study evaluations.
  • Subject will use effective contraceptive methods for the duration of the study

Exclusion Criteria:

  • Subject is HbsAg positive
  • Subject has cirrhosis score Child-Pugh B/C,
  • No previous hepatic decompensation
  • Subject has HIV-related thrombocytopenia (Platelets count < 50.000/mmc)
  • Subject has neutrophils count < 1500/mmc
  • Subject has Hb value < 11 g/dL
  • Subject has creatinine value > 1.5 mg/dL
  • Subject is pregnant or wishes to become so
  • Subject has any cause of liver disease other than chronic hepatitis C, status of liver decompensation or any other condition consistent with decompensated liver disease (bleeding from esophageal varices, signs of current bleeding, significant ascites, hepatic encephalopathy)
  • Subject is alcohol abuser (> 30 gr/die)
  • Subject has autoimmune hepatitis
  • Prior treatment with PEG-IFN or ribavirin
  • Illicit drugs abuse that in the opinion of the investigator could lead to poor compliance with the terms of the protocol (Methadone sostitution therapy allowed)
  • Active heart disease (e.g. angina, congestive heart failure, recent myocardial infarction or significant arrhythmia)
  • Subject has pre-existing severe depression, condition of severe psychiatric disorders such as suicidal ideation, suicide attempts, depression or acute psychosis
  • Subject has uncompensated diabetes
  • Subject has active opportunistic infections or major opportunistic infections during the previous 12 months
  • Subject has known hypersensitivity or contraindication to study medications
  • Subject has any other condition that in the opinion of the investigator will make the subject unsuitable for enrolment or will interfere with the subject participating in or completing the study
  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: NCT00437684

Contacts
Contact: Adriano Lazzarin, MD +39/02/26437939 adriano.lazzarin@hsr.it
Contact: Caterina Uberti-Foppa, MD +39/02/26437938 caterina.uberti@hsr.it

Locations
Italy
San Raffaele Hospital, Dep. Infectious Diseases Recruiting
Milan, Italy, 20127
Contact: Vega Rusconi    +39/02/26433646    vega.rusconi@hsr.it   
Contact: Anna De Bona, MD    +39/02/26437932    anna.debona@hsr.it   
Sub-Investigator: Caterina Uberti-Foppa, MD         
Principal Investigator: Adriano Lazzarin, MD         
Sponsors and Collaborators
IRCCS San Raffaele
Abbott
Hoffmann-La Roche
Investigators
Principal Investigator: Adriano Lazzarin, MD IRCCS San Raffaele Hospital
  More Information

No publications provided by IRCCS San Raffaele

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Adriano Lazzarin, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT00437684     History of Changes
Other Study ID Numbers: Kamon 2, NTC00437684
Study First Received: February 20, 2007
Last Updated: February 5, 2009
Health Authority: Italy: Ministry of Health

Keywords provided by IRCCS San Raffaele:
HIV/HCV
HIV and HCV coinfected patients
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hepatitis
Hepatitis A
Hepatitis C
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections
Ribavirin
Ritonavir
Peginterferon alfa-2a
Lopinavir
Reverse Transcriptase Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 11, 2014