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Comparing Continuing Tenofovir, Emtricitabine (or Lamivudine) Plus Lopinavir and Switching to Raltegravir Plus Darunavir (SPARE)

This study has been completed.
Sponsor:
Collaborator:
Ministry of Health, Labour and Welfare, Japan
Information provided by (Responsible Party):
National Center for Global Health and Medicine, Japan
ClinicalTrials.gov Identifier:
NCT01294761
First received: February 10, 2011
Last updated: March 27, 2015
Last verified: March 2015
History of Changes
  Purpose
The main objective of this clinical trial in randomizing HIV infected patients under good HIV control with tenofovir (TDF), emtricitabine (or lamivudine) plus lopinavir/ritonavir (LPV/r) into switching the regimen to raltegravir (RAL) with darunavir/ritonavir (DRV/r) or continuing the ongoing regimen to compare these two groups' estimated glomerular filtration rate (eGFR) is to investigate whether anti-HIV treatment that does not contain TDF or other reverse-transcriptase inhibitors (NTRI sparing regimen) can be protective of patients' renal functions and has the same virological efficacy in comparison with a standard treatment with TDF, or not.

Condition Intervention
HIV Infections
 Drug: Raltegravir, Darunavir/r

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Switching From Lopinavir/Ritonavir Plus Tenofovir and Emtricitabine (or Lamivudine) to Darunavir (Prezista) and Raltegravir to Evaluate Renal Function

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Center for Global Health and Medicine, Japan:

Primary Outcome Measures:
  • eGFR improvement comparison of two arms by ITT analysis [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
    To investigate whether the estimated glomerular filtration rate (eGFR) of the intervened group with RAL+DRV/r improves by 10% or more by intention to treat (ITT) analysis at the time of 48 weeks after the start of the study, or not.


Secondary Outcome Measures:
  • Virological efficacy [ Time Frame: 48 weeks up to 96 weeks ] [ Designated as safety issue: Yes ]
    Virological efficacy of the group on DRV/r+RAL

  • Renal function markers [ Time Frame: 48 weeks up to 96 weeks ] [ Designated as safety issue: Yes ]
    Serum creatinine, eGFR, uine beta-2 microglobulin, tubular resorption rate of phosphate, urine albumin, N-acetyl-beta-glucosaminidase, serum cystatin C, urine protein and urine glucose

  • Lipids [ Time Frame: 48 weeks up to 96 weeks ] [ Designated as safety issue: Yes ]
    Triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol

  • Adverse events [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
    Adverse events of each arm, symptoms and rate

  • Blood plasma concentration of RAL and DRV [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
    Blood plasma concentration level of raltegravir and darunavir among all consented and intervened cases at National Center for Global Health and Medicine

  • Discontinuation rate [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
    Discontinuation rate of each arm, reason and timing
Enrollment: 59
Study Start Date: February 2011
Study Completion Date: December 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir, Darunavir/r

An arm to change the regimen from: Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD

to: Prezista naive 2 tabs PC QD, Norvir soft-capsule 1 cap PC QD and Isentress 1 tab BID or Prezista 2 tabs PC BID and Norvir soft-capsule 1 cap PC BID, and Isentress 1 tab BID

 Drug: Raltegravir, Darunavir/r

An arm to change the regimen to: raltegravir and darunavir/ritonavir

Prezista naive 2 tabs PC QD, Norvir soft-capsule 1 cap PC QD and Isentress 1 tab BID or Prezista 2 tabs PC BID and Norvir soft-capsule 1 cap PC BID, and Isentress 1 tab BID

from: Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD

Other Name: NRTI sparing regimen
No Intervention: Tenofovir, Emtricitabine, Lopinavir/r
An arm continuing on the same regimen before the randomization as Kaletra 4 tabs QD and Truvada 1 tab QD or Kaletra 4 tabs QD, Viread 1 tab QD, Epivir300mg 1 tab (or Epivir 150mg 2 tabs) QD

Detailed Description:

Eligibility criteria are HIV infected outpatients or inpatients that are:

without history virological failure including protease inhibitors or raltegravir (disregarding whether the patient had a history of drug resistance or drug holiday, or not) taking LPV/r+TVD (or TDF+lamivudine) for longer than 15 weeks before the enrollment with HIV viral load less than 50 copies/ml for 15 weeks, including those with blips (one time episode of detectable level HIV viraemia which are proceeded and followed by undetectable viraemia).

20 years old or older Japanese willing to participate in the trial and able to agree to the informed consent. Main outcome measures are to investigate if the estimated glomerular filtration rate (eGFR) of the intervened group with RAL+DRV/r improves by 10% or more by intention to treat (ITT) analysis at the time of 48 weeks after the start of the trial.

Other outcome measures are:

virological efficacy of the group on DRV/r+RAL (after 48 weeks and up to 96 weeks) comparison of other renal function markers between the two arms: serum creatinine, urine beta-2 microglobulin, tubular resorption rate of phosphate, urine albumin, N-acetyl-beta-glucosaminidase, serum cystatin C, urine protein and urine glucose (after 48 weeks and up to 96 weeks) comparison of lipid markers between the two arms: triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol (after 48 weeks and up to 96 weeks) discontinuation rate of each arm, reason and timing of the discontinuation or the treatment change up to 96 weeks adverse events of each arm, symptoms and rate up to 96 weeks blood plasma concentration level of RAL and DRV of all consented intervened cases at National Center for Global Health and Medicine

  Eligibility
Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: HIV infected outpatients or inpatients that are

  • without history virological failure including protease inhibitors or raltegravir (disregarding whether the patient had a history of drug resistance or drug holiday, or not)
  • taking LPV/r+TVD (or TDF+lamivudine) for longer than 15 weeks before the enrollment
  • with HIV viral load less than 50 copies/ml for 15 weeks, including those with blips (one time episode of detectable level HIV viraemia which are proceeded and followed by undetectable viraemia)
  • 20 years old or older
  • Japanese
  • willing to participate in the trial and able to agree to the informed consent

Exclusion Criteria: cases applicable to any of the following will be excluded from this trial

  • HBs antigen positive within 15 weeks to the enrollment (cases confirmed as HBs antibody positive can be enrolled without HBs antigen testing)
  • malabsorption or gastrointestinal symptoms that affect absorption of the drugs, or dysphagia cases
  • clinical data within 15 weeks before the start of the trial and of the closest date to the enrollment that are GPT 2.5 times the highest of the normal range (grade 2) or eGFR less than 60ml/min (Cockcroft-Gault formula)
  • cases with opportunistic infections requiring treatment (primary and secondary preventive prophylaxis can be administrated during the study)
  • cases during pregnancy or nursing period, or with a possibility for pregnancy
  • using drugs that are prohibited to combine for drug interaction with the drugs of this trial
  • other cases that are decided by the patient's physician as not suitable for the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01294761

Locations
Japan
National Center for Global Health and Medicine
Shinjuku, Tokyo, Japan, 1628655
Sponsors and Collaborators
National Center for Global Health and Medicine, Japan
Ministry of Health, Labour and Welfare, Japan
Investigators
Principal Investigator: Shinichi Oka, MD PhD National Center for Global Health and Medicine
  More Information

Publications:

Responsible Party: National Center for Global Health and Medicine, Japan
ClinicalTrials.gov Identifier: NCT01294761     History of Changes
Other Study ID Numbers: FWA00005823-SPARE2011  UMIN000005116 
Study First Received: February 10, 2011
Last Updated: March 27, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by National Center for Global Health and Medicine, Japan:
HIV-1
AIDS
Clinical Trials, Randomized

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Lamivudine
Raltegravir Potassium
Darunavir
Emtricitabine
Lopinavir
 Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors
HIV Protease Inhibitors
Protease Inhibitors
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 29, 2016