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Lopinavir/Ritonavir Monotherapy Versus Standard Highly Active Antiretroviral Therapy (HAART) in HIV/HCV Coinfected Antiretroviral (ARV) Naive Patients Starting Treatment With Anti-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:
NCT00437476
First received: February 20, 2007
Last updated: February 5, 2009
Last verified: February 2009
History of Changes
  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 patients naive for HIV and HCV.

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


Condition Intervention Phase
HIV Infections
Hepatitis C
 Drug: LPV/r
Drug: Nucleoside Reverse Transcriptase Inhibitors
Drug: PEG-IFNa 2a
Drug: Ribavirin
 Phase 3

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • To assess if the combination of LPV/r monotherapy in association with [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • anti-HCV therapy (PEG IFN alfa 2a + Ribavirin) does not match with additional [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • toxicity induced by the combination of optimized HAART (Lopinavir/ritonavir + selected Nucs) and PEG-IFN alfa 2a+Ribavirin [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • in patients naïve for HIV and HCV [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess if LPV/r monotherapy during the HCV treatment [ Time Frame: 18 and 24 months ] [ Designated as safety issue: No ]
  • is associated with anti HIV efficacy and a better patient satisfaction [ Time Frame: 18 and 24 months ] [ Designated as safety issue: No ]
  • vs optimized HAART. [ Time Frame: 18 and 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
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 + selected NRTIs for 26 weeks, followed by LPV/r monotherapy and anti HCV drugs for 48 weeks. All the patients will be followed-up for 24 weeks after the end of anti-HCV drugs for the evaluation of SVR.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day . At the end of week 12 of combined therapy, only patients who will reach an early virological response will continue anti-HCV drugs.
 Drug: LPV/r
Lopinavir/Ritonavir 200/50 mg 2 cpr BID monotherapy - 26 weeks (A) or 24 weeks (B)
Drug: Nucleoside Reverse Transcriptase Inhibitors
NRTIs for 26 weeks (A) or 24 weeks (B)
Drug: PEG-IFNa 2a
PEG-IFNa 2a 180 mcg/week (48 weeks)
Drug: Ribavirin
Ribavirin 1-1.2 g/day (48 weeks)
Active Comparator: B
LPV/r+ selected NRTIs for 24 weeks, followed by the same HAART and anti-HCV drugs for 48 weeks. At the end of the co-treatment for HCV/HIV, each subject will be treated for HIV infection according to physician decision. All the patients will be followed-up for 24 weeks after the end of anti-HCV drugs for the evaluation of SVR.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day . At the end of week 12 of combined therapy, only patients who will reach an early virological response will continue anti-HCV drugs.
 Drug: LPV/r
Lopinavir/Ritonavir 200/50 mg 2 cpr BID monotherapy - 26 weeks (A) or 24 weeks (B)
Drug: Nucleoside Reverse Transcriptase Inhibitors
NRTIs for 26 weeks (A) or 24 weeks (B)
Drug: PEG-IFNa 2a
PEG-IFNa 2a 180 mcg/week (48 weeks)
Drug: Ribavirin
Ribavirin 1-1.2 g/day (48 weeks)

Detailed Description:

This is a pilot, randomised, open label, controlled clinical trial. All eligible patients (CD4 count > 200 and no PI resistance)will receive 26 weeks induction HAART (LPV/r + selected NUCS). At the end of induction period (Phase I), all subjects with negative HIV-RNA from at least two months, Hb > 11 g/dL and CD4 count > 350 cells/mmc will be randomised (1:1), to receive LPV/r new tabs (200/50 mg, 2 cpr BID) monotherapy (arm A) or to continue the same HAART (arm B), associated to anti-HCV therapy for other 48 weeks (Phase II). The number of subjects to recruit will be 60 subjects to start the induction-phase with the aim to randomize, at least 25 subjects in each arm of the study. The total number of subjects to randomize will be 50. The Group A: will receive LPV/r + selected NRTIs for 26 weeks, followed by LPV/r monotherapy and anti HCV drugs for 48 weeks. Group B: will receive LPV/r+ selected NRTIs for 24 weeks, followed by the same HAART and anti-HCV drugs for 48 weeks. At the end of the co-treatment for HCV/HIV, each subject will be treated for HIV infection according to physician decision.All the patients will be followed-up for 24 weeks after the end of anti-HCV drugs for the evaluation of SVR.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day . At the end of week 12 of combined therapy, only patients who will 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
  • Serologic evidence of HIV infection by HIV antibody and HIV-RNA detection
  • Serologic evidence of HCV infection by HCV antibody and HCV-RNA detection
  • Subject is naive for HIV and HCV therapy
  • Subject has active chronic hepatitis or compensated cirrhosis (Child-Pugh class A)
  • Subject has a CD4+ count > 200 cell/mm3 and <500 cell/mm3.
  • Subject has genotype available at baseline and no mutations (IAS)associated with resistance to antiretroviral drugs used.
  • Subject and partner 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 < 9 g/dL at screening and <11 g/dL at randomization
  • Subject has creatinine value > 1.5 mg/dL
  • Subject is on a HAART regimen included ddI and/or AZT
  • 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)
  • Prior treatment with PEG-IFN/ribavirin
  • Illicit drugs abuse that in the opinion of the investigator could lead to poor compliance with the terms of the protocol (maintenance treatment with methadone 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00437476

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: Giulia Gallotta, MD     +39/02/26437938     giulia.gallotta@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

Responsible Party: adriano lazzarin, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT00437476     History of Changes
Other Study ID Numbers: Kamon 1
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 Naive

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
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites

ClinicalTrials.gov processed this record on May 21, 2013