Maraviroc Switch Collaborative Study

Phase 4

Completed

• Conditions: HIV
• Interventions: Drug: Maraviroc

• Registration Number: NCT01384682
• Lead Sponsor: Kirby Institute

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-06-28
• Study First Submitted QC: 2011-06-28
• Study First Posted: 2011-06-29
• Study Start: 2011-08
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-18
• Last Update Posted: 2016-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 399

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Virological endpoints: proportion of participants with plasma HIV-1 RNA<50 copies/ml	48 weeks from randomization	A number of secondary endpoints will be examined at or through to week 48 in this protocol. These will include, but not be limited to the following: Virologic; Immunologic and biomarkers; Clinical; Metabolic and body composition; Safety; Adherence; Quality of Life and Resistance endpoints.

Trial Locations

Locations (51)

Fundacion IDEAA; 🇦🇷 Buenos Aires, Argentina

Hospital Privado- Centro Medico Cordoba; 🇦🇷 Cordoba, Argentina

Holdsworth House Medical Practice; 🇦🇺 Sydney, New South Wales, Australia

St. Vincent's Hospital; 🇦🇺 Sydney, New South Wales, Australia

Royal Prince Alfred Hospital; 🇦🇺 Sydney, New South Wales, Australia

Westmead Hospital; 🇦🇺 Sydney, New South Wales, Australia

Gladstone Road Medical Centre; 🇦🇺 Bisbane, Queensland, Australia

Brisbane Sexual Health and HIV Service (formerly AMU); 🇦🇺 Brisbane, Queensland, Australia

Nambour General Hospital; 🇦🇺 Nambour, Queensland, Australia

O'Brien Street Practice; 🇦🇺 Adelaide, South Australia, Australia

Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

FUNCEI; 🇦🇷 Buenos Aires, Ciudad de Buenos Aires, Argentina

Hospital Dr Diego Paroissien; 🇦🇷 Isidro Casanova, Provincia de Buenos Aires, Argentina

Hospital Civil de Guadalajara; 🇲🇽 Guadalajara, Jalisco, Mexico

Hospital G de Agudos JM Ramos Mejia; 🇦🇷 Buenos Aires, Ciudad de Buenos Aires, Argentina

Monash Medical Centre; 🇦🇺 Melbourne, Victoria, Australia

Hospital Nacional Prof Alejandro Posadas; 🇦🇷 El Palomar, Provincia de Buenos Aires, Argentina

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

Hospital Italiano de Buenos Aires; 🇦🇷 Buenos Aires, Ciudad de Buenos Aires, Argentina

Nagoya Medical Center; 🇯🇵 Nagoya, Japan

INCMNSZ; 🇲🇽 Mexico City, Mexico

Hospital General de Leon; 🇲🇽 Leon, Mexico

Wojewodzki Szpital Zakazny Centrum Diagnostyki i Terapii AIDS; 🇵🇱 Warsaw, Poland

CAICI; 🇦🇷 Rosario, Provincia de Santa Fe, Argentina

St. Thomas's Hospital; 🇬🇧 London, United Kingdom

Southern Alberta Clinic; 🇨🇦 Calgary, Alberta, Canada

University Health Network/Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

Canadian Immunodeficiency Research Collaborative (CIRC) lnc (Maple Leaf Clinic); 🇨🇦 Toronto, Ontario, Canada

Clinic Opus/Lori; 🇨🇦 Montreal, Quebec, Canada

Fundación Arriarán; 🇨🇱 Santiago, Santiago RM, Chile

Service Maladies infectieuses et Tropicales CHR ORLEANS La SOURCE; 🇫🇷 Orleans, France

Johann Wolfgang Goethe-University Hospital, Medical HIVCENTER; 🇩🇪 Frankfurt, Frankfurt am Main, Germany

Gemeinschaftspraxis Jessen Jessen Stein; 🇩🇪 Berlin, Germany

Dienstleistung centre ID (Baumgarten, MIB medical center for infectious diseases); 🇩🇪 Berlin, Germany

University of Bonn, Med J. Immunologische Siudienzenirale; 🇩🇪 Bonn, Germany

Klinikum der Universitat Zu Koln; 🇩🇪 Cologne, Germany

Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie, Hepatologie und Infektiologie-MX- Amb; 🇩🇪 Düsseldorf, Germany

Klinik für Immunologie und Rheumatologie, Medzinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Catalonia, Spain

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Catalonia, Spain

Hospital La Paz,; 🇪🇸 Madrid, Spain

Hospital Principe de Asturias; 🇪🇸 Madrid, Spain

Hospital Regional Carlos Haya de Málaga; 🇪🇸 Malaga, Spain

Virgen Del Rocio University Hospital; 🇪🇸 Seville, Spain

Western General Hospital; 🇬🇧 Edinburgh, Lothian, United Kingdom

Hospital Universitari i Politecnic La Fe; 🇪🇸 Valencia, Spain

Chulalongkorn University Hospital; 🇹🇭 Bangkok, Thailand

Brighton & Sussex University NHS Trust; 🇬🇧 Brighton, Sussex, United Kingdom

Coventry and Warwickshire Partnership Trust; 🇬🇧 Coventry, Warwickshire, United Kingdom

St. Mary's Hospital, Imperial College; 🇬🇧 London, United Kingdom

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Catalonia, Spain