Maraviroc Switch Collaborative Study

NCT01384682 | Completed Phase 4 DMC

• 1 other identifier: 2011-01-MAR
• Study Type: interventional
• Target: 399
• Locations: 13 countries
• Sites: 51

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.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• The comparison of the switch arms to control arm of proportions of participants with HIV RNA <200 copies/mL 48 weeks after randomisation.

  48 weeks after randomization

Secondary Outcomes (1)

• Virological endpoints: proportion of participants with plasma HIV-1 RNA<50 copies/ml

  48 weeks from randomization

Study Arms (3)

No change

NO INTERVENTION

continue their current cART regimen

Replace N(t)RTI drugs with Maraviroc

ACTIVE COMPARATOR

Replace N(t)RTI drugs with MVC at a dose of 150mg bid (MVC 300mg bid can be used at the discretion of the Investigator if the PI/r is fosamprenavir/r) and continue the PI/r

Drug: Maraviroc

Replace PI/r drugs with Maraviroc

ACTIVE COMPARATOR

Replace PI/r drugs with MVC at a dose of 300mg bid and continue 2N(t)RTI.

Drug: Maraviroc

Interventions

Maraviroc DRUG

Maraviroc is a marketed drug for the treatment of HIV-infection. Maraviroc will be supplied in two different oral dose forms, 150mg and 300mg given twice a day. The drug will be dosed according to the recommendations in the product label i.e. with PI/r the dose is 150mg bid except, Maraviroc 300mg bid can be used at the discretion of the investigator if the PI/r is fosamprenavir/r; those randomised to the 2N(t)RTI arm, will receive Maraviroc 300mg bid. Patients randomised to receive Maraviroc will be provided with bottles of Maraviroc which contain a 30-day supply.

Replace N(t)RTI drugs with Maraviroc; Replace PI/r drugs with Maraviroc

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• absolute neutrophil count (ANC) \<750 cells/µL
• haemoglobin \<8.0 g/dL
• platelet count \<50,000 cells/µL
• 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

Sponsors & Collaborators

• Kirby Institute: lead
• ViiV Healthcare: collaborator
• Pfizer: collaborator

Study Sites (51)

Fundacion IDEAA

Buenos Aires, Buenos Aires, C1405CKC, Argentina

Location

Hospital Nacional Prof Alejandro Posadas

El Palomar, Buenos Aires, 1684, Argentina

Location

Hospital Dr Diego Paroissien

Isidro Casanova, Buenos Aires, 1765, Argentina

Location

FUNCEI

Buenos Aires, Buenos Aires F.D., 1425, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, Buenos Aires F.D., C1181ACH, Argentina

Location

Hospital G de Agudos JM Ramos Mejia

Buenos Aires, Buenos Aires F.D., C1221ADC, Argentina

Location

CAICI

Rosario, Santa Fe Province, S2000PBJ, Argentina

Location

Hospital Privado- Centro Medico Cordoba

Córdoba, Argentina

Location

Holdsworth House Medical Practice

Sydney, New South Wales, 2010, Australia

Location

St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Gladstone Road Medical Centre

Bisbane, Queensland, 4101, Australia

Location

Brisbane Sexual Health and HIV Service (formerly AMU)

Brisbane, Queensland, 4000, Australia

Location

Nambour General Hospital

Nambour, Queensland, 4560, Australia

Location

O'Brien Street Practice

Adelaide, South Australia, 5000, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

Southern Alberta Clinic

Calgary, Alberta, T2R OX7, Canada

Location

University Health Network/Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Canadian Immunodeficiency Research Collaborative (CIRC) lnc (Maple Leaf Clinic)

Toronto, Ontario, ON M5G 1k2, Canada

Location

Clinic Opus/Lori

Montreal, Quebec, H3A 1T1, Canada

Location

Fundación Arriarán

Santiago, Santiago RM, Chile

Location

Service Maladies infectieuses et Tropicales CHR ORLEANS La SOURCE

Orléans, 45100, France

Location

Johann Wolfgang Goethe-University Hospital, Medical HIVCENTER

Frankfurt, Frankfurt Am Main, 60590, Germany

Location

Gemeinschaftspraxis Jessen Jessen Stein

Berlin, State of Berlin, 10777, Germany

Location

Dienstleistung centre ID (Baumgarten, MIB medical center for infectious diseases)

Berlin, 13353, Germany

Location

University of Bonn, Med J. Immunologische Siudienzenirale

Bonn, 53127, Germany

Location

Klinikum der Universitat Zu Koln

Cologne, 50937, Germany

Location

Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie, Hepatologie und Infektiologie-MX- Amb

Düsseldorf, 40225, Germany

Location

Klinik für Immunologie und Rheumatologie, Medzinische Hochschule Hannover

Hanover, 30625, Germany

Location

Mater Misericordiae University Hospital

Dublin, Dublin, 7, Ireland

Location

Nagoya Medical Center

Nagoya, 460-0001, Japan

Location

Hospital Civil de Guadalajara

Guadalajara, Jalisco, 44280, Mexico

Location

Hospital General de Leon

León, 37320, Mexico

Location

INCMNSZ

Mexico City, Mexico

Location

Wojewodzki Szpital Zakazny Centrum Diagnostyki i Terapii AIDS

Warsaw, Warsaw, 01-201, Poland

Location

Hospital Germans Trias i Pujol

Badalona, Catalonia, 08916, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

Location

Hospital Regional Carlos Haya de Málaga

Málaga, Malaga, 29010, Spain

Location

Hospital La Paz,

Madrid, 28046, Spain

Location

Hospital Principe de Asturias

Madrid, 28805, Spain

Location

Virgen Del Rocio University Hospital

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Chulalongkorn University Hospital

Bangkok, Bangkok, 10330, Thailand

Location

St. Mary's Hospital, Imperial College

London, London, W2, United Kingdom

Location

St. Thomas's Hospital

London, London, United Kingdom

Location

Western General Hospital

Edinburgh, Lothian, United Kingdom

Location

Brighton & Sussex University NHS Trust

Brighton, Sussex, BN21ES, United Kingdom

Location

Coventry and Warwickshire Partnership Trust

Coventry, Warwickshire, CV 1 4FS, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 27048747 DERIVED

• 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.

  PMID: 23596247 DERIVED

Related Links

• Kirby Institute for infection and immunity in society homepage - click here for more information on the MARCH study.

MeSH Terms

Interventions

Maraviroc

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David A Cooper, AO

  Kirby Institute, University of New South Wales

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2011
• First Posted: June 29, 2011
• Study Start: August 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 20, 2016

Record last verified: 2016-01

Locations

ME (3); FR (1); AR (8); JP (1); CA (4); IE (1); DE (7); CL (1); PL (1); AU (10); ES (8); GB (5); TH (1)