MARCH Renal Substudy (MARCHrenal)

Maraviroc Switch Collaborative Study Renal Substudy

Chronic kidney disease (CKD) is an emerging problem in patients with treated HIV. Antiretroviral therapy associated renal dysfunction has been predominantly described in terms of reduced glomerular filtration (eGFR). Proteinuria is a key component of CKD and may occur in the absence of significant reductions in eGFR. This substudy is an exploration of changes in urinary protein excretion in a randomised, open-label study to evaluate the efficacy and safety of MVC as a switch for either nucleoside or nucleotide analogue reverse transcriptase inhibitors (N(t)RTI) or boosted protease inhibitors (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 combination antiretroviral therapy (cART).

Study Overview

• Status: Completed
• Conditions: Proteinuria; HIV
• Intervention / Treatment: Drug: arm 1 nucleotide analogue reverse transcriptase inhibitors and boosted protease inhibitors; Drug: Arm 2 boosted protease inhibitors and maraviroc; Drug: Arm 3 nucleotide analogue reverse transcriptase inhibitors and maraviroc

Detailed Description

The aim of this substudy of MARCH is to characterize the changes in protein and salt excretion through the kidney utilising the randomised arms of the parent study MARCH. The investigators hypothesize there will be an improvement in proteinuria in those switching to maraviroc containing regimens.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Ciudad de Buenos Aires
    • Buenos Aires, Ciudad de Buenos Aires, Argentina, C1181ACH
      • Hospital Italiano de Buenos Aires
    • Buenos Aires, Ciudad de Buenos Aires, Argentina, C1221ADC
      • Hospital General de Agudos J M Ramos Mejia
    • Buenos Aires, Ciudad de Buenos Aires, Argentina, C1405CKC
      • Fundacion IDEAA
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St. Vincent's Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4000
      • Brisbane Sexual Health and HIV Service
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2R OX7
      • Southern Alberta Clinic
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network - Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1T1
      • Clinic Opus/Lori
• Germany
  • Cologne, Germany, 50937
    • Klinikum der Universität zu Köln
  • Dusseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie, Hepatologie und Infektiologie, MX-Ambulanz
• Japan
  • Nagoya, Japan, 460-0001
    • Nagoya Medical Center
• Mexico
  • Tlalpan DF
    • Mexico City, Tlalpan DF, Mexico, 14000
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn University Hospital
• United Kingdom
  • Lothian
    • Edinburgh, Lothian, United Kingdom
      • Western General Hospital
  • Sussex
    • Brighton, Sussex, United Kingdom
      • Brighton & Sussex University NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of written, informed consent for participation in the substudy
• Enrolled into the substudy either at or before the week 0 visit of the main study

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NRTI + PI; arm 1	Drug: arm 1 nucleotide analogue reverse transcriptase inhibitors and boosted protease inhibitors; NRTI + PI; Other Names: lamivudine; fosamprenavir; emtricitabine; lopinavir; ritonavir; zidovudine; abacavir; tenofovir; atazanavir; darunavir
Active Comparator: PI + maraviroc; arm 2	Drug: Arm 2 boosted protease inhibitors and maraviroc; PI + maraviroc; Other Names: maraviroc; fosamprenavir; lopinavir; ritonavir; atazanavir; darunavir
Active Comparator: NRTI + maraviroc; arm 3	Drug: Arm 3 nucleotide analogue reverse transcriptase inhibitors and maraviroc; NRTI + maraviroc; Other Names: lamivudine; maraviroc; emtricitabine; zidovudine; abacavir; tenofovir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in proteinuria and albuminuria between baseline and week 96	To compare the change in protein and albumin excretion as measured by the urine PCR and ACR through the kidneys between the randomised and standard of care (control) arm of MARCH.	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in renal tubular function between baseline and week 96	To evaluate the following aspects of renal function at baseline and changes within and between study groups: Tubular function defined as proximal tubular function; ascending thick loop of Henle; distal tubular function; volume and renal potassium handling;; Non-tubular function i.e. eGFR; Urine albumin:creatinine ratio;; Determine factors associated with renal dysfunction within the cohort e.g. demographics, HIV related, HIV-treatment related, co-morbidities, concomitant medication (such as ACE inhibitors and ARB; PI/r co-administered with TDF); TDF use;	96 weeks

Collaborators and Investigators

• Sponsor: Kirby Institute
• Investigators: Principal Investigator: Waldo Belloso, MD, Hospital Italiano de Buenos Aires; Principal Investigator: Mark Kelly, MD, Brisbane Sexual Health and HIV Service

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 27, 2012
• First Submitted That Met QC Criteria: July 10, 2012
• First Posted (Estimate): July 11, 2012

Study Record Updates

• Last Update Posted (Estimate): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 18, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: HIV; proteinuria
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Urination Disorders; Proteinuria; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Tenofovir; Emtricitabine; Ritonavir; Lopinavir; Lamivudine; Zidovudine; Protease Inhibitors; Maraviroc; Reverse Transcriptase Inhibitors; Darunavir; Atazanavir Sulfate; Abacavir; Dideoxynucleosides; Fosamprenavir; HIV Protease Inhibitors
• Other Study ID Numbers: MARCH-Kirby renal