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

Sponsor:	IRCCS San Raffaele
Collaborators:	Abbott Hoffmann-La Roche
Information provided by:	IRCCS San Raffaele
ClinicalTrials.gov Identifier:	NCT00437684

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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:

MedlinePlus related topics: AIDS Hepatitis Hepatitis C

Drug Information available for: Ribavirin Ritonavir Lopinavir Peginterferon Alfa-2a

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 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
A: Experimental 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
B: Active Comparator 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

Arms

Assigned Interventions

A: Experimental

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

B: Active Comparator

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

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

Responsible Party:	IRCCS San Raffaele ( Adriano Lazzarin )
Study ID Numbers:	Kamon 2, NTC00437684
Study First Received:	February 20, 2007
Last Updated:	February 5, 2009
ClinicalTrials.gov Identifier:	NCT00437684 History of Changes
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:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Liver Diseases
Slow Virus Diseases
Flaviviridae Infections
Molecular Mechanisms of Pharmacological Action
Ribavirin
Hepatitis, Viral, Human
Infection
Anti-Retroviral Agents
Lopinavir
Therapeutic Uses
Hepatitis C
Retroviridae Infections

HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
Hepatitis
Digestive System Diseases
HIV Infections
Ritonavir

ClinicalTrials.gov processed this record on February 08, 2010