Trial Outcomes & Findings for Pilot Study of a Raltegravir Based NRTI Sparing Regimen (NCT NCT00814879)

Last Updated: 2016-02-04

Results Overview

Virologic failure was defined by protocol as a plasma HIV RNA \>50 c/mL on 2 consecutive occasions \>7 days apart or \> 10 000 c/mL on one occasion (in the absence of an intercurrent infection or recent immunization).

Recruitment status

COMPLETED

Study phase

Target enrollment

60 participants

Primary outcome timeframe

48 Weeks

Results posted on

2016-02-04

Participant Flow

A total of 60 patients were randomized in this pilot study; 30 in each arm. Two patients randomized to stay on their N(t)NRTIs+PIr regimen were randomization failures as the patients did not for return for their baseline visit.

Participant milestones

Participant milestones
Measure	N(t)RTI(s) + PI/r N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
By Week 24 STARTED	28	30
By Week 24 COMPLETED	27	29
By Week 24 NOT COMPLETED	1	1
By Week 48 STARTED	27	29
By Week 48 COMPLETED	25	26
By Week 48 NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	N(t)RTI(s) + PI/r N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
By Week 24 Cancer Diagnosis	1	0
By Week 24 Incarceration	0	1
By Week 48 Lost to Follow-up	2	2
By Week 48 Death	0	1

Baseline Characteristics

Pilot Study of a Raltegravir Based NRTI Sparing Regimen

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	N(t)NRTI + Plr n=28 Participants N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=30 Participants Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID	Total n=58 Participants Total of all reporting groups
Age, Continuous	48.5 years STANDARD_DEVIATION 9.8 • n=99 Participants	48.0 years STANDARD_DEVIATION 9.7 • n=107 Participants	48.2 years STANDARD_DEVIATION 9.6 • n=206 Participants
Sex: Female, Male Female	5 Participants n=99 Participants	6 Participants n=107 Participants	11 Participants n=206 Participants
Sex: Female, Male Male	23 Participants n=99 Participants	24 Participants n=107 Participants	47 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	6 Participants n=99 Participants	9 Participants n=107 Participants	15 Participants n=206 Participants
Race (NIH/OMB) White	21 Participants n=99 Participants	20 Participants n=107 Participants	41 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Region of Enrollment United States	28 participants n=99 Participants	30 participants n=107 Participants	58 participants n=206 Participants

PRIMARY outcome

Timeframe: 48 Weeks

Outcome measures

Outcome measures
Measure	N(t)RTI(s) + PI/r n=25 Participants N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=26 Participants Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
Number of Patients Reaching Virologic Failure at Week 48.	2 participants	3 participants

SECONDARY outcome

Timeframe: 48 weeks

Outcome measures

Outcome measures
Measure	N(t)RTI(s) + PI/r n=25 Participants N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=26 Participants Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
Number of Patients With < 400 Copies HIV RNA/mL at Week 48	22 participants	21 participants

SECONDARY outcome

Timeframe: Weeks 24

Outcome measures

Outcome measures
Measure	N(t)RTI(s) + PI/r n=27 Participants N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=29 Participants Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
CD4+ Cell Count	599.4 cells/mm^3 Standard Deviation 276.1	710.0 cells/mm^3 Standard Deviation 37.80

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	N(t)RTI(s) + PI/r n=25 Participants N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=26 Participants Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
CD4+ Cell Count	596.6 cells/mm^3 Standard Deviation 289.1	665.9 cells/mm^3 Standard Deviation 365.4

SECONDARY outcome

Timeframe: baseline, week 24, week 48

Total cholersterol (mg/dL)

Outcome measures

Outcome measures
Measure	N(t)RTI(s) + PI/r n=25 Participants N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=26 Participants Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
Cholesterol Baseline	166.25 mg/dL Standard Deviation 41.58	178.83 mg/dL Standard Deviation 46.97
Cholesterol Week 24	168.07 mg/dL Standard Deviation 43.77	169.65 mg/dL Standard Deviation 41.39
Cholesterol Week 48	167.41 mg/dL Standard Deviation 41.19	174.48 mg/dL Standard Deviation 37.12

SECONDARY outcome

Timeframe: baseline and 48 weeks

mean change in total bilirubin from baseline

Outcome measures

Outcome measures
Measure	N(t)RTI(s) + PI/r n=25 Participants N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=26 Participants Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
Mean Change in Total Bilirubin (mg/dL) From Baseline	-0.15 mg/dL Standard Deviation 0.85	0.37 mg/dL Standard Deviation 1.39

Adverse Events

N(t)RTI(s) + PI/r

Serious events: 3 serious events

Other events: 26 other events

Deaths: 0 deaths

RAL + ATV

Serious events: 6 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	N(t)RTI(s) + PI/r n=28 participants at risk N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=30 participants at risk Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
Reproductive system and breast disorders Pregnancy	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Endocrine disorders Hyperglycemia	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 3 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Skin and subcutaneous tissue disorders Cellulitis	7.1% 2/28 • Number of events 2 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Respiratory, thoracic and mediastinal disorders Aspiration Pneumonia	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 2 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Cancer	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Gastrointestinal disorders Diarrhea	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Gastrointestinal disorders Mesenteric Panniculitis	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Psychiatric disorders Suicidal Ideation	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Immune system disorders Death	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.

Other adverse events

Additional Information

Dr. Michael J. Kozal

Yale University School of Medicine: Internal Medicine: Infectious Diseases: AIDS Care Program / Viral Hepatitis Program

Phone: (203)737-4040

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	N(t)RTI(s) + PI/r n=28 participants at risk N(t)RTI(s) based backbone \& PI/r Standard treatment regimen: N(t)RTI(s) based backbone plus ritonavir boosted PI	RAL + ATV n=30 participants at risk Raltegravir (RAL) 400mg BID + atazanavir (ATV) 300 mg BID Raltegravir: 400 mg BID Atazanavir: 300 mg BID
Psychiatric disorders Anxiety	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	13.3% 4/30 • Number of events 4 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Respiratory, thoracic and mediastinal disorders CAP- Community Acquired Pneumonia	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 2 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Gastrointestinal disorders Constipation	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	6.7% 2/30 • Number of events 2 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Respiratory, thoracic and mediastinal disorders Cough	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Psychiatric disorders Depression	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Gastrointestinal disorders Diarrhea	10.7% 3/28 • Number of events 3 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	13.3% 4/30 • Number of events 6 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Nervous system disorders Dizziness	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Skin and subcutaneous tissue disorders Edema	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Respiratory, thoracic and mediastinal disorders DOE- Dyspnea on Exertion	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
General disorders Fatigue	10.7% 3/28 • Number of events 3 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Infections and infestations Fever	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Skin and subcutaneous tissue disorders Folliculitis	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Gastrointestinal disorders GERD	7.1% 2/28 • Number of events 2 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
General disorders Headache	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	10.0% 3/30 • Number of events 3 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
General disorders Myalgias	0.00% 0/28 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Gastrointestinal disorders Nausea	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	10.0% 3/30 • Number of events 3 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
General disorders Night Sweats	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
General disorders General Pain	14.3% 4/28 • Number of events 7 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	10.0% 3/30 • Number of events 6 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
General disorders Sinus Congestion	3.6% 1/28 • Number of events 3 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Infections and infestations Sinusitis	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	3.3% 1/30 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Infections and infestations Upper Respiratory Infection	10.7% 3/28 • Number of events 4 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	10.0% 3/30 • Number of events 4 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Renal and urinary disorders Urinary Tract Infection	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	6.7% 2/30 • Number of events 2 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
Gastrointestinal disorders Vomiting	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	6.7% 2/30 • Number of events 2 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
General disorders Weight Loss	3.6% 1/28 • Number of events 1 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	0.00% 0/30 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.
General disorders Other	85.7% 24/28 • Number of events 77 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.	80.0% 24/30 • Number of events 90 • Adverse events were assesses across the duration of the study through week 48. Serious adverse events were those that resulted in either hospitalization, death or pregnancy.