Long Term Treatment Interruptions

This study has been completed.
Sponsor:
Information provided by:
A.O. Ospedale Papa Giovanni XXIII
ClinicalTrials.gov Identifier:
NCT00433056
First received: February 7, 2007
Last updated: April 24, 2008
Last verified: April 2008
  Purpose

LOTTI study Centers

This a multicenter, multinational study.

Clinical phase: III

Objectives

The primary objective is to compare efficacy and safety of continuing a conventional HAART in chronically infected HIV patients with a therapeutic strategy based on long term, immunologically driven treatment interruptions.

Secondary objectives are:

  • To verify the risk of developing viral resistance
  • To verify the effect of the two strategies on metabolic parameters
  • To verify the possibility to steadily discontinue antiretroviral therapy in patients who started it with baseline immunological values higher than those currently recommended by international guidelines for HIV treatment
  • To identify predictive variables of the possibility to safely discontinue antiretroviral therapy
  • To verify the dynamic of CD4+ cell loss and HIV replication after treatment interruption

Number of Patients: A total of 320 patients.

Study design:

Controlled, Randomized, Open study The study will last 5 years

Treatment arms:

Patients will be randomized in a ratio 1:1 to one of the two treatment arms Control group continuing the ongoing therapy STI group performing long term CD4 guided structured treatment interruptions In the STI arm patients will stay off therapy until their CD4 count will drop < 350 cells/mcL (one measurement will be considered sufficient). At that time point patients will resume the HAART regimen they were assuming before STI and will continue HAART until they CD4 count will raise > 600 cells/mcL (at least 2 consecutive measurements 2 months apart) and their HIV-RNA will drop below the detection limit of 50 copies/ml (one measurement will be considered sufficient). When both the CD4 count and the viral load will be within these pre-set values they will stop therapy again. There is no limit to the number of interruptions and re-start cycles during the study period

End points:

The primary end-point for the evaluation of the main objective of the study will be clinical. The primary outcome measure will be based on the occurrence of a clinical end-point defined as: disease progression (occurrence of any AIDS defining event), death for any cause or the occurrence of clinical events requiring hospital admission

The secondary objectives of the study will be evaluated on the basis of:

  • Mean variation of blood cholesterol and triglycerides from baseline values.
  • Development of lipodystrophy or modification of a pre-existing lipodystrophy
  • Time off therapy.
  • Variation of CD4 counts and HIV-RNA levels
  • Genotypic tests to be performed in the case of HIV-RNA > 1000 copies/ml while on therapy for at least 4 months or one month after each treatment interruption.

Statistics:

The study is powered to evaluate equivalence between the two strategies under the assumption that, in the control arm, the primary end-point would be observed in a proportion of subjects < 7% and that the same proportion in the STI arm would not exceed 10% with a maximum allowed 95%CI of 12%. 320 patients will be needed for alfa = 5% and 1-beta = 80%. The primary analysis will be made according to the intention-to-treat approach and therefore no correction for eventual drop outs is needed. In addition, a secondary per-protocol analysis will be performed.


Condition Intervention Phase
HIV Infections
AIDS
Other: STI
Drug: stable HAART
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: Strategic, Long Term, Immunologically Driven Treatment Interruptions in Patients on Effective HAART: A Controlled, Randomized Study

Resource links provided by NLM:


Further study details as provided by A.O. Ospedale Papa Giovanni XXIII:

Primary Outcome Measures:
  • The primary outcome will be clinical response: Death, ADE, pathology requiring hospital admission [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mean variation of blood cholesterol and triglycerides from baseline values. Development of lipodystrophy or modification of a pre-existing lipodystrophy [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Time off therapy, variation of CD4 counts and HIV-RNA levels [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Genotypic tests to be performed in the case of HIV-RNA > 1000 copies/ml while on therapy for at least 4 months or one month after each treatment interruption. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 320
Study Start Date: January 2004
Arms Assigned Interventions
Experimental: 1
STI
Other: STI
CD4 guided treatment interruption
Active Comparator: 2
stable HAART, Any registered regimen containing NRTIs (AZT or D4T or 3TC or TDF or DDI), NNRTIs (EFV or NVP) or PIs (RTV-boosted ATV; IDV; LPV, fosAPV, SQV; unboosted ATV or NFV)is allowed according to international guidelines
Drug: stable HAART
continuous therapy

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 17 years
  • Informed consent signed
  • Effective ongoing treatment (HIV-RNA < 50 copies/ml). Treatment must be based on any triple drug therapy. Patients must be on the same steady therapy for at least 3 months.
  • Current CD4 cell count above 600 cells/mcL and nadir of CD4 cell count > 200 cells/mcL

Exclusion Criteria:

  • Childbearing or breastfeeding. Women of childbearing potential will be asked to adopt effective contraceptive methods or behaviors
  • Any ongoing grade 4 (WHO) AE or laboratory abnormality with the exclusion of cholesterol, triglycerides for which a grade 3 (AHA) level will be considered an exclusion criteria.
  • Previous diagnosis of AIDS
  • Patients with HBV coinfection on active anti-HIV treatment with either lamivudine and/or tenofovir
  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: NCT00433056

Locations
Italy
Ospedali Riuniti
Bergamo, BG, Italy, 24128
Sponsors and Collaborators
A.O. Ospedale Papa Giovanni XXIII
Investigators
Principal Investigator: Franco Maggiolo, MD Ospedali Riuniti, Bergamo
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00433056     History of Changes
Other Study ID Numbers: LOTTI
Study First Received: February 7, 2007
Last Updated: April 24, 2008
Health Authority: Italy: Istituto Superiore di sanità

Keywords provided by A.O. Ospedale Papa Giovanni XXIII:
STI
HIV
CD4
HIV-RNA
HAART

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
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

ClinicalTrials.gov processed this record on October 16, 2014