Clinical trial NCT00379405: Saquinavir/Ritonavir in Single Therapy as Maintenance Treatment
Official title: Open-label, Comparative and Randomised Pilot Study to Evaluate the Efficacy and Safety of Saquinavir/Ritonavir in Single Therapy vs Standard HAART Therapy as Maintenance Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Saquinavir/ritonavir
Single therapy
Virological efficacy
Safety
HIV-1
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
First posted: 2006-09-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study the efficacy of Saquinavir/Ritonavir when given in single therapy as maintenance therapy, compared to standard HAART therapies.

Detailed description: Different therapeutic strategies have been investigated to improve adherence to treatment and reduce toxicity. Both the reduction in the number of doses and the number of daily tablets have led to an improvement in therapeutic compliance. Similarly, the administration of new treatment regimens with a reduced number of tablets a day and without NTRI may be clinically useful in improving compliance with HAART and limiting NTRI-associated toxicity. These would comprise combinations of a PI, boosted with ritonavir, plus a non-Nucleoside and single therapy with PIs boosted with ritonavir.

In this regard, the results obtained with lopinavir/ritonavir and with atazanavir/ritonavir are very promising and open up a possible channel of research with other PIs boosted with low doses of ritonavir.

There are other PIs whose antiretroviral efficacy has also been demonstrated, such as saquinavir, but whose economic cost is much lower. Furthermore, saquinavir has a low toxicity profile, and the availability of saquinavir 500 mg facilitates comfortable administration, since it makes it possible to reduce the number of daily tablets to more than half.

Moreover, it is important to take into account that the incidence of mutations that confer resistance to saquinavir on patients that fail on combinations including this PI is very low, which makes it possible to reuse the drug in future treatment regimens or salvage patients with other PI All these characteristics (high intrinsic potency, low number of tablets, low toxicity, low potential of selection of resistant viral strains in combination with ritonavir, and low economic cost) make single therapy with the new formulation of saquinavir, boosted with low doses of ritonavir, a possible therapeutic option as maintenance strategy in HIV-infected patients with maintained suppression of the viral load.

Eligibility criteria: Inclusion Criteria:

* Patients infected by HIV-1 (at least one documented positive Western-Blot).
* Age \> 18 years.
* Patients on antiretroviral treatment (standard HAART therapy) for at least six months.
* HIV-1 plasma viral load \<50 copies/mL (documented in at least two determinations performed over the six months prior to the inclusion visit).
* Patients without evidence of previous virological failure to IP
* Absence of opportunistic infections and/or tumours in the three months prior to inclusion.
* Subject able to follow the treatment period, without any suspicion of poor adherence during previous antiretroviral treatments.
* Signature of the informed consent.

Exclusion Criteria:

* Suspicion of unsuitable antiretroviral treatment compliance.
* Documented existence of any of the primary mutations in the protease gene or 3 or more of the following: L10F/I/R/V, K20M/R, M36I/V, I54L/T/V, L63P, A71T/V , V82A/F/T/S, I84A/V OR L90M.
* Known allergic hypersensitivity to any of the investigational drugs or any similar drug.
* Hepatic tests (AST, ALT, GGT) \> or equal to 5 times the upper limit of normality during the three months prior to the screening visit
* Presence of renal impairment (creatinine \> or equal to 1.5 times the upper limit of normality).
* Pregnancy or breastfeeding. Refusal to use reliable contraceptive methods during the study period.
* Participation in another clinical trial wich entail the antiretroviral treatment modification.

Primary outcomes:
measure: Virological response: Viral Load
timeFrame: weeks 24 and 48
Secondary outcomes:
measure: CD4 and CD8 lymphocyte count.
timeFrame: weeks 24 and 48
measure: Physical Exploration: including weight, height, index waist/hip (the abdominal perimeter is measured between the last floating rib and the iliac crest), assessment of changes in body fat distribution,...
timeFrame: weeks 24 and 48
measure: Karnofsky Index.
timeFrame: weeks 24 and 48
measure: Adverse events.
timeFrame: during the 48 weeks of follow-up
measure: Trough plasma concentrations of Saquinavir.
timeFrame: during the 48 weeks of follow-up
measure: Lipid study in plasma (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides)
timeFrame: during the 48 weeks of follow-up
measure: Serology for Hepatitis B and C virus.
timeFrame: at baseline visit
measure: Assessment of treatment adherence.
timeFrame: at baseline and weeks 4, 12, 24, 36 and 48
measure: Assessment of quality of life (by means of the MOS-HIV questionnaire).
timeFrame: at baseline and weeks 4, 12, 24, 36 and 48
measure: Genotype if virological failure.
timeFrame: at any time of study if it is necessary
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol University Hospital
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Sant Pau.
Study officials:
affiliation: Hospital Universitari Germans Trias i Pujol. Badalona (Barcelona)
name: Clotet Bonaventura, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitari Germans Trias i Pujol. Badalona. (Barcelona)
name: Negredo Eugenia, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitari Germans Trias i Pujol. Badalona. (Barcelona)
name: Echeverria Patricia, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitari Germans Trias i Pujol. Badalona. (Barcelona)
name: Molto Jose, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Sant Pau
name: Pere Domingo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: