Clinical trial NCT01384682: Maraviroc Switch Collaborative Study
Official title: Randomised, Openlabel Study Evaluating Efficacy and Safety of Maraviroc as a Switch for Either NRTI or PI/r in HIV-1 Infected Individuals With Stable, Well-Controlled Plasma HIV-RNA While Taking Their First N(t)RTI + PI/r Regimen of cART
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Lead sponsor: Kirby Institute
Sponsor class: OTHER_GOV
Collaborators: name: ViiV Healthcare
name: Pfizer
First posted: 2011-06-29
Enrollment: 399
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: MARCH is an international, multicentre trial planning to enroll 380 HIV-1 infected patients who are currently on 2N(t)RTI + PI/r regimen and virologically suppressed. Participants will be randomized (1:2:2) to one of three treatment groups: to continue their current treatment regimen, maraviroc dose at 150 mg twice daily with PI/r, or maraviroc at 300 mg twice daily with 2N(t)RTI. As the participants population have HIV RNA \<200 copies/mL, the phenotypic assessment of tropism cannot be used to determine tropism, instead we will employ the genotypic assessment of tropism by sequencing the V3 loop of the HIV envelope. The main aim of this study is to investigate whether switching to maraviroc, in combination with either RTI or PI/r, is as good at keeping the HIV viral load undetectable as the combination of RTI with PI/r. The other aim is to see if switching to these combinations with maraviroc will improve some of the side effects that can be seen when people take combination therapy including RTI and PI/r.

The study hypothesis is that in stable, virologically suppressed (plasma HIV-RNA \<200 copies/mL) patients with no history of prior virological failure, a switch to either MVC dosed at 300mg twice daily (bid) combined with the same 2N(t)RTI backbone regimen or MVC dosed at 150mg twice daily (bid) with the current PI/r (or 300mg bid at the discretion of the investigator if the PI/r is fosamprenavir/r) provides similar (non-inferior) antiretroviral efficacy compared to continuation of the current 2N(t)RTI + PI/r regimen.


Eligibility criteria: Inclusion Criteria:

* Documented HIV-1 infection by a licensed diagnostic test at any time prior to study entry
* Age \>18 years
* HIV-1 RNA \<200 copies/mL plasma for at least 24 weeks
* Stable (\>24 weeks) ART including two N(t)RTIs and a PI/r
* No evidence of any primary HIV genotypic mutations in HIV reverse transcriptase or protease for all patients with available resistance testing results conducted prior to cART and/or during viral rebound/failure
* Provision of written, informed consent.

Exclusion Criteria:

* CXCR4 or CCR5/CXCR4 dual tropic HIV tropism or a non-reportable tropism result based on assessment using proviral DNA
* Anticipated need to modify current cART regimen for toxicity management in the next 6 months
* The following laboratory criteria,

  1. absolute neutrophil count (ANC) \<750 cells/µL
  2. haemoglobin \<8.0 g/dL
  3. platelet count \<50,000 cells/µL
  4. serum AST, ALT \>5 x upper limit of normal (ULN)
* Active hepatitis B co-infection
* Pregnant women or nursing mothers
* Current use of any prohibited medications as described in product specific information.
* Hypersensitivity to soy or peanuts
* Acute therapy for serious infection or other serious medical illness (in the judgement of the site Principal Investigator) requiring systemic treatment and/or hospitalisation
* Use of immunomodulators (e.g. systemic corticosteroids, recombinant interleukin-2, interferon) within 30 days prior to screening
* Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the study
* Patients unlikely to be able to remain in follow-up for the protocol-defined period
* Prisoners or subjects who are compulsorily detained (involuntary incarcerated).

Primary outcomes:
measure: The comparison of the switch arms to control arm of proportions of participants with HIV RNA <200 copies/mL 48 weeks after randomisation.
timeFrame: 48 weeks after randomization
Secondary outcomes:
measure: Virological endpoints: proportion of participants with plasma HIV-1 RNA<50 copies/ml
timeFrame: 48 weeks from randomization
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: FUNCEI
state: Ciudad de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Ciudad de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital G de Agudos JM Ramos Mejia
state: Ciudad de Buenos Aires
city: El Palomar
country: Argentina
facility: Hospital Nacional Prof Alejandro Posadas
state: Provincia de Buenos Aires
city: Isidro Casanova
country: Argentina
facility: Hospital Dr Diego Paroissien
state: Provincia de Buenos Aires
city: Rosario
country: Argentina
facility: CAICI
state: Provincia de Santa Fe
city: Buenos Aires
country: Argentina
facility: Fundacion IDEAA
city: Cordoba
country: Argentina
facility: Hospital Privado- Centro Medico Cordoba
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Bisbane
country: Australia
facility: Gladstone Road Medical Centre
state: Queensland
city: Brisbane
country: Australia
facility: Brisbane Sexual Health and HIV Service (formerly AMU)
state: Queensland
city: Nambour
country: Australia
facility: Nambour General Hospital
state: Queensland
city: Adelaide
country: Australia
facility: O'Brien Street Practice
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Calgary
country: Canada
facility: Southern Alberta Clinic
state: Alberta
city: Toronto
country: Canada
facility: University Health Network/Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Canadian Immunodeficiency Research Collaborative (CIRC) lnc (Maple Leaf Clinic)
state: Ontario
city: Montreal
country: Canada
facility: Clinic Opus/Lori
state: Quebec
city: Santiago
country: Chile
facility: Fundación Arriarán
state: Santiago RM
city: Orleans
country: France
facility: Service Maladies infectieuses et Tropicales CHR ORLEANS La SOURCE
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe-University Hospital, Medical HIVCENTER
state: Frankfurt am Main
city: Berlin
country: Germany
facility: Gemeinschaftspraxis Jessen Jessen Stein
city: Berlin
country: Germany
facility: Dienstleistung centre ID (Baumgarten, MIB medical center for infectious diseases)
city: Bonn
country: Germany
facility: University of Bonn, Med J. Immunologische Siudienzenirale
city: Cologne
country: Germany
facility: Klinikum der Universitat Zu Koln
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie, Hepatologie und Infektiologie-MX- Amb
city: Hannover
country: Germany
facility: Klinik für Immunologie und Rheumatologie, Medzinische Hochschule Hannover
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Nagoya
country: Japan
facility: Nagoya Medical Center
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara
state: Jalisco
city: Leon
country: Mexico
facility: Hospital General de Leon
city: Mexico City
country: Mexico
facility: INCMNSZ
city: Warsaw
country: Poland
facility: Wojewodzki Szpital Zakazny Centrum Diagnostyki i Terapii AIDS
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Catalonia
city: Madrid
country: Spain
facility: Hospital La Paz,
city: Madrid
country: Spain
facility: Hospital Principe de Asturias
city: Malaga
country: Spain
facility: Hospital Regional Carlos Haya de Málaga
city: Seville
country: Spain
facility: Virgen Del Rocio University Hospital
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Bangkok
country: Thailand
facility: Chulalongkorn University Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Lothian
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University NHS Trust
state: Sussex
city: Coventry
country: United Kingdom
facility: Coventry and Warwickshire Partnership Trust
state: Warwickshire
city: London
country: United Kingdom
facility: St. Mary's Hospital, Imperial College
city: London
country: United Kingdom
facility: St. Thomas's Hospital
Study officials:
affiliation: Kirby Institute, University of New South Wales
name: David A Cooper, AO
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pett SL, Amin J, Horban A, Andrade-Villanueva J, Losso M, Porteiro N, Sierra Madero J, Belloso W, Tu E, Silk D, Kelleher A, Harrigan R, Clark A, Sugiura W, Wolff M, Gill J, Gatell J, Fisher M, Clarke A, Ruxrungtham K, Prazuck T, Kaiser R, Woolley I, Arnaiz JA, Cooper D, Rockstroh JK, Mallon P, Emery S; Maraviroc Switch (MARCH) Study Group. Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study. Clin Infect Dis. 2016 Jul 1;63(1):122-32. doi: 10.1093/cid/ciw207. Epub 2016 Apr 5.
citation: Tu E, Swenson LC, Land S, Pett S, Emery S, Marks K, Kelleher AD, Kaye S, Kaiser R, Schuelter E, Harrigan R; MARCH Laboratory Group and the MARCH Study Group. Results of external quality assessment for proviral DNA testing of HIV tropism in the Maraviroc Switch collaborative study. J Clin Microbiol. 2013 Jul;51(7):2063-71. doi: 10.1128/JCM.00510-13. Epub 2013 Apr 17.