Clinical trial NCT01348308: Immuno-stimulation With Maraviroc Combined to Antiretroviral Therapy in Advanced Late Diagnosed HIV-1 Infected Patients
Official title: Optimized Phase III Trial of Immuno-stimulation With Maraviroc, a CCR5 (Chemokine Receptor 5) Antagonist, Combined With Anti Retroviral Therapy in Advanced, Late Diagnosed HIV-1 Infected Patients With an AIDS-defining Event and/or CD4 (Cluster of Differentiation 4) Counts Below 200 Cells/mm³. ANRS 146 OPTIMAL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
AIDS
Keywords: Late diagnosed HIV-1 infected patients
AIDS-defining events
Immune restoration
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Pfizer
First posted: 2011-05-05
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the OPTIMAL study is to demonstrate that the adjunction of Maraviroc to a combination of antiretroviral therapy in naive and late diagnosed HIV-1 infected patients counts may accelerate the kinetics of immune restoration and decrease the risk of disease progression and death.

It is a randomized, versus placebo, double-blind trial, conducted in France, Spain and Italy.


Eligibility criteria: Inclusion Criteria:

* Confirmed HIV-1 infection (ELISA and Western Blot tests positive)
* CD4+ T lymphocytes below or equal 200/mm³ or previous AIDS-defining-illness at diagnosis
* Patient naïve from any antiretroviral
* In women, use of a contraceptive method, and lack of actual pregnancy
* Patients with a coverage from social health
* After informed consent

Exclusion Criteria:

* Current pregnancy, lack of contraceptive method, breast-feeding
* Current active tuberculosis (either suspected, diagnosed)
* Ongoing malignancies except cutaneous Kaposi's sarcoma. Patients with a previous cancer considered as cured for at least 6 months could be included in the study
* Current or previous severe cardiac failure, chronic respiratory disease, renal or liver insufficiency; any life-threatening organ failure
* Cognitive impairment, psychiatric disorders, severe depressive affects, unadapted behavior
* Use of cytostatic drugs, immunosuppressive agents, steroids
* PMN (polymorphonuclear neutrophil) below 750/mm³, platelets below 50,000/mm³, haemoglobin below 10 g/dL; ASAT (aspartate aminotransferase), ALAT (alanine aminotransferase) or bilirubin over 2.5 ULN; lipase over 2 ULN (Upper limit of normal), serum creatinine over 1.5 ULN; proteinuria over 1g/L; INR (International Normalized Ratio) abnormal
* Current or previous, during the 3 last months, use of immunomodulatory agents (G-CSF (granulocyte colony stimulating factor), IL-2 (Interleukin-2), GM-CSF (Granulocyte Macrophage colony stimulating factor), interferons, pentoxifylline)
* Hypersensitivity to peanut and /or soy products

Primary outcomes:
measure: To demonstrate the clinical benefit of the adjunction of Maraviroc to a combination of antiretroviral therapy defined as decrease of clinical events
timeFrame: From Week 0 to Week 72
Secondary outcomes:
measure: Safety evaluation and Clinical, Immunological and pharmacological evaluation
timeFrame: From Week 0 to Week 72
Other outcomes:
Locations:
city: Creteil
country: France
facility: Hôpital Henri Mondor
Study officials:
affiliation: APHP, Hopital Henri Mondor, Creteil, France
name: Yves Levy, MD, PhD
role: STUDY_CHAIR
affiliation: APHP, Hopital Henri Mondor, Creteil, France
name: Jean-Daniel Lelievre, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: INSERM U943 and Univerité Pierre et Marie Curie
name: Dominique Costagliola, PhD
role: STUDY_DIRECTOR
References:
citation: Levy Y, Lelievre JD, Assoumou L, Aznar E, Pulido F, Tambussi G, Crespo M, Meybeck A, Molina JM, Delaugerre C, Izopet J, Peytavin G, Cardon F, Diallo A, Lancar R, Beniguel L, Costagliola D. Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial. Ann Intern Med. 2020 Mar 3;172(5):297-305. doi: 10.7326/M19-2133. Epub 2020 Feb 11.