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Trial record 12 of 23 for:    " December 21, 2011":" January 20, 2012"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression

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ClinicalTrials.gov Identifier: NCT01511809
Recruitment Status : Completed
First Posted : January 19, 2012
Results First Posted : November 24, 2014
Last Update Posted : February 5, 2016
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Castagna Antonella, Ospedale San Raffaele

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 Infection
Intervention Drug: Atazanavir/ritonavir monotherapy
Enrollment 117
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Atazanavir/Ritonavir Monotherapy Atazanavir/Ritonavir Triple Therapy
Hide Arm/Group Description

Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy

Atazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.

Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone
Period Title: Overall Study
Started 58 59
Completed 51 52
Not Completed 7 7
Arm/Group Title Atazanavir/Ritonavir Monotherapy Atazanavir/Ritonavir Triple Therapy Total
Hide Arm/Group Description

Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy

Atazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.

Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone Total of all reporting groups
Overall Number of Baseline Participants 51 52 103
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 51 participants 52 participants 103 participants
41.4
(35.4 to 47.7)
41.7
(36.6 to 49.8)
41.5
(35.6 to 48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 52 participants 103 participants
Female
9
  17.6%
7
  13.5%
16
  15.5%
Male
42
  82.4%
45
  86.5%
87
  84.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Italy Number Analyzed 51 participants 52 participants 103 participants
51 52 103
nadir CD4+   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm3
Number Analyzed 51 participants 52 participants 103 participants
274
(221 to 355)
278
(183 to 364)
276
(211 to 361)
[1]
Measure Description: Lowest CD4+ value among those recorded since the first HIV positive test up to the start of MODAt study
Years of antiretroviral treatment  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 51 participants 52 participants 103 participants
25
(16 to 47)
25
(18 to 54)
25
(17 to 53)
HIV-1 RNA <50 copies/ml   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Months
Number Analyzed 51 participants 52 participants 103 participants
20
(10 to 49)
18
(12 to 49)
19
(11 to 49)
[1]
Measure Description: Quantitative value of HIV-1 RNA copies/ml in plasma. HIV-1 RNA below 50 copies/ml (detection limit) is an indicator of efficacy of the antiretroviral therapy
HIV-RNA at ARV start  
Median (Inter-Quartile Range)
Unit of measure:  copies/mL
Number Analyzed 51 participants 52 participants 103 participants
79399
(31046 to 183613)
42630
(9696 to 123700)
59062
(10834 to 165850)
CD4+  
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm3
Number Analyzed 51 participants 52 participants 103 participants
599
(457 to 774)
570
(417 to 735)
575
(432 to 744)
HCV coinfection  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 51 participants 52 participants 103 participants
Present 11 10 21
Absent 40 42 82
1.Primary Outcome
Title Proportion of Patients With Treatment Failure (TF)
Hide Description Proportion of patients with treatment failure defined as having one of the following events: confirmed viral rebound (CVR) or treatment discontinuation for any cause. CVR was established when 2 consecutive viral load values (HIV-1 RNA)>50 copies/mL occurred within 2 weeks during follow-up. In case of CVR, patients treated with atazanavir/ritonavir monotherapy had to re-introduce their previous 2NRTIs (re-intensification) and, if not suppressed (HIV-1 RNA <50 copies /ml) after 12 weeks, discontinued from the study. Re-intensification was considered as treatment failure in the primary analysis conducted according to the intention-to-treat principle (intention-to-treat analysis with re-intensification equal failure, ITT=Failure) while it was not in the secondary analysis (intention-to-treat analysis with re-intensification equal success, ITT=Success).
Time Frame Up to week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atazanavir/Ritonavir Monotherapy Atazanavir/Ritonavir Triple Therapy
Hide Arm/Group Description:

Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy

Atazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.

Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone
Overall Number of Participants Analyzed 51 52
Measure Type: Number
Unit of Measure: percentage of patients
ITT=Failure analysis 27.5 15.4
ITT=Success analysis 7.9 15.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atazanavir/Ritonavir Monotherapy, Atazanavir/Ritonavir Triple Therapy
Comments

Here are reported the results of the 48-week interim analyses according to the intention-to-treat (ITT) principle. ITT=F (with re-intensification=failure) and the ITT=S (with re-intensification=success) treatment failure results are shown.

Based on the efficacy data review, in June 2013, an independent Data and Safety Monitoring Board (DSMB) recommended to stop further patients’ enrolment and to follow-up the enrolled patients until 96 weeks, after having signed an updated informed consent.

Type of Statistical Test Non-Inferiority or Equivalence
Comments A lower limit of the 95% confidence interval of the difference between the two proportions of treatment failure (triple therapy-monotherapy) below the pre-specified margin of non-inferiority of -10% established inferiority. A sample size of 342 patients (171 per treatment arm) provided 80% power (one-sided, alpha 0.05) to establish non-inferiority of ATV/r monotherapy as compared to ATV/r triple therapy with an overall treatment failure (TF) rate of 15% at week 48.
Method of Estimation Estimation Parameter difference between TF proportions
Estimated Value 15
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Efficacy and Safety
Hide Description

Proportion of pts with confirmed virological and treatment failure at w96. Change in CD4 cell counts.

Occurrence of viral resistance to atazanavir in pts with confirmed virologic failure.

Proportion of pts with adverse events, with ≥grade 2 adverse events or abnormal laboratory tests, proportion of pts with side effects leading to discontinuation.

Body fat redistribution and vertebral and femoral bone mineral density. Adherence changes; changes in HIV-associated neurocognitive disorders. Difference in levels of activated Tcells and pro-inflammatory cytokines between treatment groups.

Time Frame week 96
Outcome Measure Data Not Reported
Time Frame Up to week 48
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Atazanavir/Ritonavir Monotherapy Atazanavir/Ritonavir Triple Therapy
Hide Arm/Group Description

Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy

Atazanavir/ritonavir monotherapy: Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.

Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone
All-Cause Mortality
Atazanavir/Ritonavir Monotherapy Atazanavir/Ritonavir Triple Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Atazanavir/Ritonavir Monotherapy Atazanavir/Ritonavir Triple Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   2/51 (3.92%)   0/52 (0.00%) 
Cardiac disorders     
acute coronary stenosis *  1/51 (1.96%)  0/52 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
left basal pneumonia *  1/51 (1.96%)  0/52 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Atazanavir/Ritonavir Monotherapy Atazanavir/Ritonavir Triple Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   1/51 (1.96%)   7/52 (13.46%) 
Hepatobiliary disorders     
acute hepatitis *  1/51 (1.96%)  1/52 (1.92%) 
cholecystitis due to cholelithiasis *  0/51 (0.00%)  1/52 (1.92%) 
Renal and urinary disorders     
nephrolitiasis *  0/51 (0.00%)  2/52 (3.85%) 
hyperuricemia *  0/51 (0.00%)  1/52 (1.92%) 
gross haematuria with proteinuria *  0/51 (0.00%)  2/52 (3.85%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Antonella Castagna
Organization: Ospedale San Raffaele
Phone: 00390226437934
Publications:
Responsible Party: Castagna Antonella, Ospedale San Raffaele
ClinicalTrials.gov Identifier: NCT01511809     History of Changes
Other Study ID Numbers: MODAt
First Submitted: January 13, 2012
First Posted: January 19, 2012
Results First Submitted: November 7, 2014
Results First Posted: November 24, 2014
Last Update Posted: February 5, 2016