Staccato: A Trial of CD4 Guided Treatment Interruption, Compared to Continuous Treatment, for HIV Infection

NCT ID: NCT00113126

Last Updated: 2006-11-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 526 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2005-10-31

Brief Summary

Treatment of HIV repairs the immune system, but continuous treatment is expensive and causes side effects. Would it not be better to treat intermittently, e.g. stop treatment when the immune system has recovered, and start again only when damage reappears? That is the question which STACCATO proposes to answer.

Approximately 500 patients were recruited for this trial from 2002 to 2004. One third were treated continuously; in two thirds, the treatment was interrupted whenever the CD4 count, a measure of immune recovery, exceeded 350. At the end of 2005, the two treatment groups will be compared in order to see which fared better regarding amount of drugs used, side effects, CD4 counts, and development of resistance to treatment.

Detailed Description

Continuous treatment has been very successful in diminishing the diseases and deaths caused by HIV. However, continuous treatment is expensive. Intermittent treatment will always cost less than continuous treatment, and therefore has the potential to facilitate access to highly active antiretroviral therapy (HAART) in developing countries. HAART also causes many undesirable effects. Intermittent treatment decreases exposure to drugs and is therefore expected to decrease side effects.

STACCATO is a randomised trial of intermittent versus continuous anti-retroviral treatment. At least 600 patients on HAART, with viremia below 50 copies/ml and CD4 count above 350 cells/ml were randomised to one of two arms, in 1:2 proportions:

• Arm 1: Continuation (control) arm: Drugs are continued or changed according to current guidelines and good clinical practice.
• Arm 2: CD4-guided arm: Drugs discontinued and reintroduced according to CD4 counts, with HAART being administered only if CD4 count is < 350 cells/ml.

Randomized treatment will continue during an average of approximately 2 years, and will be followed by a period of 12 to 24 weeks' continuous treatment, for patients in both arms.

Endpoints: The amount of drugs used, side effects, viremia and CD4 counts, number of clinical events, at the end of the randomized treatment period, and again 12 to 24 weeks later. A subproject will study the effect of treatment interruption on resistance development, mutations in proviral DNA and proviral DNA levels.

Conditions

HIV Infection; AIDS

Keywords

Scheduled treatment interruptions; STI

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Treatment interruption

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• CD4 lymphocyte count above 350/microliter and viral HIV1-RNA below 50 copies/ml on antiretroviral treatment.

Exclusion Criteria

• Virologic failure of treatment. Failure of treatment defined as a treatment switch motivated by high viral loads on treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Geneva

OTHER

Sponsor Role: lead

Principal Investigators

Bernard Hirschel, MD

Role: STUDY_CHAIR

Infectious Diseases Unit - University Hospital

Locations

Infectious Diseases Unit - University Hospital

Geneva, , Switzerland

Countries

Switzerland

References

Ananworanich J, Nuesch R, Le Braz M, Chetchotisakd P, Vibhagool A, Wicharuk S, Ruxrungtham K, Furrer H, Cooper D, Hirschel B, Bernasconi E, Cavassini M, Ebnother C, Fagard C, Genne D, Khanna N, Perrin L, Phanupak P, Ubolyam S, Vernazza P, Yerly S; Swiss HIV Cohort Study. Failures of 1 week on, 1 week off antiretroviral therapies in a randomized trial. AIDS. 2003 Oct 17;17(15):F33-7. doi: 10.1097/00002030-200310170-00001.

Reference Type: BACKGROUND

PMID: 14523294 (View on PubMed)

Ananworanich J, Gayet-Ageron A, Le Braz M, Prasithsirikul W, Chetchotisakd P, Kiertiburanakul S, Munsakul W, Raksakulkarn P, Tansuphasawasdikul S, Sirivichayakul S, Cavassini M, Karrer U, Genne D, Nuesch R, Vernazza P, Bernasconi E, Leduc D, Satchell C, Yerly S, Perrin L, Hill A, Perneger T, Phanuphak P, Furrer H, Cooper D, Ruxrungtham K, Hirschel B; Staccato Study Group; Swiss HIV Cohort Study. CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial. Lancet. 2006 Aug 5;368(9534):459-65. doi: 10.1016/S0140-6736(06)69153-8.

Reference Type: RESULT

PMID: 16890832 (View on PubMed)

Calmy A, Gayet-Ageron A, Montecucco F, Nguyen A, Mach F, Burger F, Ubolyam S, Carr A, Ruxungtham K, Hirschel B, Ananworanich J; STACCATO Study Group. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS. 2009 May 15;23(8):929-39. doi: 10.1097/qad.0b013e32832995fa.

Reference Type: DERIVED

PMID: 19425222 (View on PubMed)

Ananworanich J, Nuesch R, Cote HC, Kerr SJ, Hill A, Jupimai T, Laopraynak N, Saenawat S, Ruxrungtham K, Hirschel B. Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine--a Staccato trial substudy. J Antimicrob Chemother. 2008 Jun;61(6):1340-3. doi: 10.1093/jac/dkn097. Epub 2008 Mar 12.

Reference Type: DERIVED

PMID: 18339636 (View on PubMed)

Other Identifiers

SHCS # 356

Identifier Type: -

Identifier Source: org_study_id