Raltegravir Added to Stable HAART in HIV-1 Infected Subjects With Viral Suppression and Low CD4 Recovery - Full Text View

Sponsor:	The Huesped Foundation
Collaborator:	Merck
Information provided by:	The Huesped Foundation
ClinicalTrials.gov Identifier:	NCT00562510

Purpose

This is a Phase 3, randomized, double blinded, placebo-controlled study designed to compare the safety, tolerability, antiviral activity and immunological effect of raltegravir added to a previously stable HAART regimen in the treatment of HIV-1 infected subjects with undetectable viraemia and low CD4 recovery.

HYPOTHESIS:

Adding raltegravir to a stable HAART in patients with undetectable plasma viral load and low CD4 recovery will result in further viral suppression and therefore higher CD4 recovery.

Condition	Intervention	Phase
HIV Infections	Drug: Raltegravir Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	A Phase 3, Randomized, Double Blinded, Placebo Controlled Study of Raltegravir Added to Stable HAART in HIV-1 Infected Subjects With Viral Suppression and Low CD4 Recovery

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Raltegravir

U.S. FDA Resources

Further study details as provided by The Huesped Foundation:

Primary Outcome Measures:

Proportion of subjects increasing CD4 count > 50 cells/mm³. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients achieving plasma HIV-RNA < 5 copies/ml. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Proportion of subjects increasing CD4 count > 50 cells/mm³. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Proportion of patients achieving CD4 count > 250 cells/mm3 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Proportion of patients achieving an increase of 5 percentual points in CD4 percentage [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Median change from baseline in CD4 count. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
Proportion of patients maintaining HIV RNA <50 copies/ml. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	August 2008
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Raltegravir: Experimental	Drug: Raltegravir Raltegravir 400 mg BID added to stable HAART
Raltegravir matching placebo: Placebo Comparator	Drug: Placebo Placebo BID added to stable HAART

Detailed Description:

Although HAART has reduced the morbidity and mortality from HIV-1 infection, some patients experience a discordant response characterized by HIV-1 RNA plasma levels below the limit of detection and low CD4 T-cell recovery (immunologic discordant responders). At present, recommendations for the clinical management of patients with discordant responses to antiretroviral therapy are largely based on observational, uncontrolled data.

The effect on CD4 count of adding raltegravir in already undetectable patients has not yet been evaluated.

The primary purpose of this study is to assess the ability of the HIV-1 integrase inhibitor, raltegravir, added to a stable HAART, to increase CD4 count in patients with undetectable plasma viral load and low CD4 recovery.

Eligibility

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

Criteria

Inclusion Criteria:

Documented HIV-1 infection.
Subject has voluntarily signed and dated an informed consent form.
Documented sustained HIV RNA < 50 copies/ml (two consecutive pVL < 50 copies/ml, first VL > 12 months before the screening date) without documentation of HIV RNA > 50 copies/ml for at least 12 months while on previous stable HAART (PS_HAART).
HIV RNA < 50 copies/ml at screening.
Subject is currently receiving an antiretroviral regimen which has not changed for at least 12 months.
CD4 count < 200 cells/ mm3 AND CD4 increase < 100 cells/ mm3 in the last 12 months.
Subject's vital signs, physical examination and laboratory results do not exhibit evidence of acute illness.
Negative serum or urine pregnancy test and willing to use acceptable means of contraception.

Exclusion Criteria:

Patient is receiving tenofovir DF AND didanosine as a component of the background antiretroviral therapy.
Patient has a current (active) diagnosis of acute hepatitis due to any cause OR chronic hepatitis B and/or C WITH aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)>2.5 x upper limit of normal (ULN) AND/OR is likely to require treatment in the next year.
Subject has significant history of cardiac, renal, neurologic, psychiatric, oncologic, metabolic, or hepatic disease or any condition that, in the investigators opinion, could compromise the subject's safety or adherence to the trial protocol.
Subject has a currently active AIDS defining illness (category C conditions according to the CDC Classification System for HIV infection 1993) within 30 days of screening. Subjects who are on stable maintenance therapy for an opportunistic infection may be enrolled.
Life expectancy < 1 year according to the judgment of the investigator.
Screening laboratory analysis show any of the following abnormal laboratory results:
- Hemoglobin < 8.0 g/dL
- Absolute neutrophil count < 750 cells/µL
- Platelet count < 50,000 mm3
Use of any investigational agents within 30 days prior to screening.
Previous use of integrase inhibitors.
Use of immunosuppressive drugs, cytokine inhibitors or other cytokines in the last year.
Continuous use of systemic corticoids for more than a month in the last year or any use in the last 3 months.
Subject has an ongoing history of substance abuse or psychiatric illness.
Subject is pregnant or breast-feeding.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562510

Contacts

Contact: Carina T Cesar, MD

54 11 4981 7777 ext 14

carina.cesar@huesped.org.ar

Locations

Argentina
Fundacion Huesped	Recruiting
Buenos Aires, Argentina, 1202
Contact: Carina T Cesar, MD 54 11 4981 7777 ext 114 carina.cesar@huesped.org.ar
Principal Investigator: Pedro E Cahn, MD, PhD
Sub-Investigator: Carina T Cesar, MD
Sub-Investigator: Alejandro J Krolewiecki, MD
Sub-Investigator: Patricia L Patterson, MD
Sub-Investigator: Omar G Sued, MD
Sub-Investigator: Lorena Abusamra, MD
Sub-Investigator: Ana M Gun, bioch

Sponsors and Collaborators

The Huesped Foundation

Merck

Investigators

Principal Investigator:

Pedro E Cahn, MD, PhD

Fundacion Huesped

More Information

Additional Information:

Fundacion Huesped This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	The Huesped Foundation ( The Huesped Foundation )
Study ID Numbers:	FH-RAL-01, ANMAT-1-4721846/07-6
Study First Received:	November 21, 2007
Last Updated:	August 4, 2009
ClinicalTrials.gov Identifier:	NCT00562510 History of Changes
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by The Huesped Foundation:

HIV-1 infection
raltegravir
immune discordance
HIV-1 infection
treatment experienced

Additional relevant MeSH terms:

Communicable Diseases
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Immune System Diseases
Acquired Immunodeficiency Syndrome
Infection

Immunologic Deficiency Syndromes
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on February 08, 2010