Trial Outcomes & Findings for Post-Licensure Safety Study of ISENTRESS™ (Raltegravir) in a United States Managed Care Network (MK-0518-268) (NCT NCT01078246)
NCT ID: NCT01078246
Last Updated: 2018-08-22
Results Overview
All new malignancies occurring during the risk period, including Acquired Immune Deficiency Syndrome (AIDS)-defining and non-AIDS-defining malignancies, were identified through the Kaiser Permanente cancer registries. The registry data was supplemented by the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations to identify cancers that would not be captured through the cancer registries (e.g. cutaneous Kaposi's sarcoma).The AIDS-defining malignancies reported for any cohort were invasive cervical cancer, Kaposi's sarcoma, and non-Hodgkin lymphoma. Incidence is reported as unadjusted, crude rates.
COMPLETED
7124 participants
Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)
2018-08-22
Participant Flow
The analyses in this study are based on data collected from a cohort of human immunodeficiency virus (HIV-1)-infected participants in a setting of routine clinical care at the Kaiser Permanente medical centers in California, United States. Participants could contribute data to more than one cohort, but no overlap in follow-up time was allowed.
Participant milestones
| Measure |
Raltegravir Cohort Only
Participants with HIV-1 infection who received raltegravir (RAL) on or after 12 October 2007 (the market authorization date in the United States) (Raltegravir Cohort). These participants contributed data to the Raltegravir Cohort only.
|
Historical and Raltegravir Cohorts Only
Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), and 2) received RAL on or after 12 October 2007 (Raltegravir Cohort). These participants contributed data to the Historical and Raltegravir Cohorts only.
|
Historical Cohort Only
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort). These participants contributed data to the Historical Cohort only.
|
Historical and Concurrent Cohorts Only
Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), and 2) received therapy with a new non-RAL antiretroviral therapy after 12 October 2007 (Concurrent Cohort). These participants contributed data to the Historical and Concurrent Cohorts only.
|
Concurrent Cohort Only
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007 (Concurrent Cohort). These participants contributed data to the Concurrent Cohort only.
|
Concurrent and Raltegravir Cohorts Only
Participants with HIV-1 infection who 1) received therapy with a new non-RAL antiretroviral therapy on or after 12 October 2007 (Concurrent Cohort), and 2) received RAL after 12 October 2007 (Raltegravir Cohort). These participants contributed data to the Concurrent and Raltegravir Cohorts only.
|
Historical, Concurrent and Raltegravir Cohorts
Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), 2) received therapy with a new non-RAL antiretroviral therapy on or after 12 October 2007 (Concurrent Cohort), and 3) received RAL after 12 October 2007 (Raltegravir Cohort). These participants contributed data to all three cohorts.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
1041
|
405
|
1963
|
152
|
3310
|
231
|
22
|
|
Overall Study
COMPLETED
|
1041
|
405
|
1963
|
152
|
3310
|
231
|
22
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Post-Licensure Safety Study of ISENTRESS™ (Raltegravir) in a United States Managed Care Network (MK-0518-268)
Baseline characteristics by cohort
| Measure |
Raltegravir Cohort Only
n=1041 Participants
Participants with HIV-1 infection who received raltegravir (RAL) on or after 12 October 2007 (the market authorization date in the United States) (Raltegravir Cohort). These participants contributed data to the Raltegravir Cohort only.
|
Historical and Raltegravir Cohorts Only
n=405 Participants
Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), and 2) received RAL on or after 12 October 2007 (Raltegravir Cohort). These participants contributed data to the Historical and Raltegravir Cohorts only.
|
Historical Cohort Only
n=1963 Participants
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort). These participants contributed data to the Historical Cohort only.
|
Historical and Concurrent Cohorts Only
n=152 Participants
Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), and 2) received therapy with a new non-RAL antiretroviral therapy after 12 October 2007 (Concurrent Cohort). These participants contributed data to the Historical and Concurrent Cohorts only.
|
Concurrent Cohort Only
n=3310 Participants
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007 (Concurrent Cohort). These participants contributed data to the Concurrent Cohort only.
|
Concurrent and Raltegravir Cohorts Only
n=231 Participants
Participants with HIV-1 infection who 1) received therapy with a new non-RAL antiretroviral therapy on or after 12 October 2007 (Concurrent Cohort), and 2) received RAL after 12 October 2007 (Raltegravir Cohort). These participants contributed data to the Concurrent and Raltegravir Cohorts only.
|
Historical, Concurrent and Raltegravir Cohorts
n=22 Participants
Participants with HIV-1 infection who 1) received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007 (Historical Cohort), 2) received therapy with a new non-RAL antiretroviral therapy on or after 12 October 2007 (Concurrent Cohort), and 3) received RAL after 12 October 2007 (Raltegravir Cohort). These participants contributed data to all three cohorts.
|
Total
n=7124 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
48.2 Years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
49.2 Years
STANDARD_DEVIATION 10.0 • n=7 Participants
|
45.8 Years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
44.9 Years
STANDARD_DEVIATION 9.9 • n=4 Participants
|
43.0 Years
STANDARD_DEVIATION 11.5 • n=21 Participants
|
46.8 Years
STANDARD_DEVIATION 12.4 • n=8 Participants
|
45.5 Years
STANDARD_DEVIATION 9.9 • n=8 Participants
|
45.0 Years
STANDARD_DEVIATION 11.1 • n=24 Participants
|
|
Sex: Female, Male
Female
|
121 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
195 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
340 Participants
n=21 Participants
|
33 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
757 Participants
n=24 Participants
|
|
Sex: Female, Male
Male
|
920 Participants
n=5 Participants
|
364 Participants
n=7 Participants
|
1768 Participants
n=5 Participants
|
129 Participants
n=4 Participants
|
2970 Participants
n=21 Participants
|
198 Participants
n=8 Participants
|
18 Participants
n=8 Participants
|
6367 Participants
n=24 Participants
|
PRIMARY outcome
Timeframe: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)Population: The analysis includes all eligible participants.
All new malignancies occurring during the risk period, including Acquired Immune Deficiency Syndrome (AIDS)-defining and non-AIDS-defining malignancies, were identified through the Kaiser Permanente cancer registries. The registry data was supplemented by the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations to identify cancers that would not be captured through the cancer registries (e.g. cutaneous Kaposi's sarcoma).The AIDS-defining malignancies reported for any cohort were invasive cervical cancer, Kaposi's sarcoma, and non-Hodgkin lymphoma. Incidence is reported as unadjusted, crude rates.
Outcome measures
| Measure |
Raltegravir Cohort
n=1699 Participants
Participants with HIV-1 infection who received RAL on or after 12 October 2007. Participants from the Historical Cohort and the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
Historical Cohort
n=2542 Participants
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007. These participants were eligible for inclusion in the Concurrent and Raltegravir Cohorts.
|
Concurrent Cohort
n=3715 Participants
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007. Participants from the Historical Cohort were eligible for inclusion in the Concurrent Cohort. Participants from the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
|---|---|---|---|
|
Incidence of AIDS-defining and Non-AIDS-defining Malignancy
AIDS-defining Malignancy
|
13.0 Events per 1000 person-years of followup
Interval 9.6 to 16.3
|
8.9 Events per 1000 person-years of followup
Interval 5.7 to 12.2
|
9.3 Events per 1000 person-years of followup
Interval 7.4 to 11.2
|
|
Incidence of AIDS-defining and Non-AIDS-defining Malignancy
Non-AIDS-defining Malignancy
|
18.2 Events per 1000 person-years of followup
Interval 14.3 to 22.1
|
9.1 Events per 1000 person-years of followup
Interval 5.8 to 12.3
|
10.3 Events per 1000 person-years of followup
Interval 8.3 to 12.3
|
PRIMARY outcome
Timeframe: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)Population: The analysis includes all eligible participants.
Hepatic events occurring during the risk period were identified through computer-stored records of laboratory values, outpatient visits, Emergency Department visits, and hospitalizations. Significant hepatic events were identified based on algorithms utilizing a combination of diagnoses, procedures, and laboratory results. Incidence is reported as unadjusted, crude rates.
Outcome measures
| Measure |
Raltegravir Cohort
n=1699 Participants
Participants with HIV-1 infection who received RAL on or after 12 October 2007. Participants from the Historical Cohort and the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
Historical Cohort
n=2542 Participants
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007. These participants were eligible for inclusion in the Concurrent and Raltegravir Cohorts.
|
Concurrent Cohort
n=3715 Participants
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007. Participants from the Historical Cohort were eligible for inclusion in the Concurrent Cohort. Participants from the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
|---|---|---|---|
|
Incidence of Clinically Important Hepatic Events
|
19.0 Events per 1000 person-years of followup
Interval 14.9 to 23.0
|
25.0 Events per 1000 person-years of followup
Interval 19.6 to 30.5
|
17.1 Events per 1000 person-years of followup
Interval 14.5 to 19.7
|
PRIMARY outcome
Timeframe: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)Population: The analysis includes all eligible participants.
Significant skin events (e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis) occurring during the risk period were identified through the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations. The identification of potential significant skin events was based on algorithms utilizing a combination of diagnoses, procedures and/or medications. Surveillance of outpatient visits was limited to rashes coded as drug-related and requiring use of steroid (e.g. prednisone) administration. Incidence is reported as unadjusted, crude rates.
Outcome measures
| Measure |
Raltegravir Cohort
n=1699 Participants
Participants with HIV-1 infection who received RAL on or after 12 October 2007. Participants from the Historical Cohort and the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
Historical Cohort
n=2542 Participants
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007. These participants were eligible for inclusion in the Concurrent and Raltegravir Cohorts.
|
Concurrent Cohort
n=3715 Participants
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007. Participants from the Historical Cohort were eligible for inclusion in the Concurrent Cohort. Participants from the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
|---|---|---|---|
|
Incidence of Clinically Important Skin Events
|
40.6 Events per 1000 person-years of followup
Interval 34.4 to 46.8
|
69.8 Events per 1000 person-years of followup
Interval 60.4 to 79.2
|
63.6 Events per 1000 person-years of followup
Interval 58.2 to 69.1
|
PRIMARY outcome
Timeframe: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)Population: The analysis includes all eligible participants.
Significant muscle events (e.g. rhabdomyolysis) occurring during the risk period were identified through the use of computer-stored records of laboratory values, outpatient visits, Emergency Department visits and hospitalizations. The identification of potential significant muscle events was based on algorithms utilizing a combination of diagnoses, procedures and/or laboratory results for creatinine kinase. The number of muscle events did not meet the threshold for statistical analysis per protocol. Incidence is reported as unadjusted, crude rates.
Outcome measures
| Measure |
Raltegravir Cohort
n=1699 Participants
Participants with HIV-1 infection who received RAL on or after 12 October 2007. Participants from the Historical Cohort and the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
Historical Cohort
n=2542 Participants
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007. These participants were eligible for inclusion in the Concurrent and Raltegravir Cohorts.
|
Concurrent Cohort
n=3715 Participants
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007. Participants from the Historical Cohort were eligible for inclusion in the Concurrent Cohort. Participants from the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
|---|---|---|---|
|
Incidence of Clinically Important Muscle Events
|
3.4 Events per 1000 person-years of followup
Interval 1.7 to 5.1
|
3.3 Events per 1000 person-years of followup
Interval 1.4 to 5.3
|
1.5 Events per 1000 person-years of followup
Interval 0.7 to 2.3
|
PRIMARY outcome
Timeframe: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)Population: The analysis includes all eligible participants.
Lipodystrophy (e.g. lipoatrophy, facial wasting) occurring during the risk period was identified through the use of computer-stored records of outpatient visits, Emergency Department visits and hospitalizations. The identification of potential lipodystrophy was based on two coded diagnoses codes indicative of lipodystrophy appearing at least 6 months apart over the course of patient care, the identification of interventions to treat such conditions (e.g. sculptra therapy), or procedural codes for Computerized Tomography indicating incident neck or abdominal lipoaccumulation. Incidence is reported as unadjusted, crude rates.
Outcome measures
| Measure |
Raltegravir Cohort
n=1699 Participants
Participants with HIV-1 infection who received RAL on or after 12 October 2007. Participants from the Historical Cohort and the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
Historical Cohort
n=2542 Participants
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007. These participants were eligible for inclusion in the Concurrent and Raltegravir Cohorts.
|
Concurrent Cohort
n=3715 Participants
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007. Participants from the Historical Cohort were eligible for inclusion in the Concurrent Cohort. Participants from the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
|---|---|---|---|
|
Incidence of Lipodystrophy
|
20.6 Events per 1000 person-years of followup
Interval 15.9 to 25.4
|
35.6 Events per 1000 person-years of followup
Interval 28.9 to 42.4
|
9.2 Events per 1000 person-years of followup
Interval 7.2 to 11.1
|
SECONDARY outcome
Timeframe: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)Population: The analysis includes all eligible participants.
Significant cardiovascular events occurring during the risk period were identified through the use of computer-stored records and defined as inpatient events based on algorithms that utilize a combination of diagnosis and/or procedure codes. The identification of potential significant cardiovascular events was based on the occurrence of major adverse cardiovascular events (MACE) which include acute myocardial infarction (MI), ischemic stroke, unstable angina, revascularization (e.g. percutaneous coronary intervention (PCI) and coronary bypass graft surgery (CABG)), and cardiovascular death. Incidence is reported as unadjusted, crude rates.
Outcome measures
| Measure |
Raltegravir Cohort
n=1699 Participants
Participants with HIV-1 infection who received RAL on or after 12 October 2007. Participants from the Historical Cohort and the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
Historical Cohort
n=2542 Participants
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007. These participants were eligible for inclusion in the Concurrent and Raltegravir Cohorts.
|
Concurrent Cohort
n=3715 Participants
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007. Participants from the Historical Cohort were eligible for inclusion in the Concurrent Cohort. Participants from the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
|---|---|---|---|
|
Incidence of Clinically Important Cardiovascular Events
|
6.7 Events per 1000 person-years of followup
Interval 4.4 to 9.1
|
6.4 Events per 1000 person-years of followup
Interval 3.7 to 9.1
|
4.0 Events per 1000 person-years of followup
Interval 2.8 to 5.3
|
SECONDARY outcome
Timeframe: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)Population: The analysis includes all eligible participants.
All-cause mortality occurring during the risk period was identified through the use of computer-stored records of Emergency Department visits, hospitalizations, and state death certificates. Deaths were identified from administrative Kaiser Permanente databases, including Kaiser Permanente regional research and respective state(s) mortality files as well as the Social Security Administrative files. Incidence is reported as unadjusted, crude rates.
Outcome measures
| Measure |
Raltegravir Cohort
n=1699 Participants
Participants with HIV-1 infection who received RAL on or after 12 October 2007. Participants from the Historical Cohort and the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
Historical Cohort
n=2542 Participants
Participants with HIV-1 infection who received antiretroviral therapy (non-RAL) between 1 January 2005 and 11 October 2007. These participants were eligible for inclusion in the Concurrent and Raltegravir Cohorts.
|
Concurrent Cohort
n=3715 Participants
Participants with HIV-1 infection who received therapy with a new non-RAL antiretroviral therapy after 12 October 2007. Participants from the Historical Cohort were eligible for inclusion in the Concurrent Cohort. Participants from the Concurrent Cohort were eligible for inclusion in the Raltegravir Cohort.
|
|---|---|---|---|
|
Incidence of All-cause Mortality
|
16.9 Events per 1000 person-years of followup
Interval 13.3 to 20.6
|
18.4 Events per 1000 person-years of followup
Interval 13.7 to 23.0
|
7.7 Events per 1000 person-years of followup
Interval 6.0 to 9.4
|
Adverse Events
Raltegravir Cohort
Historical Cohort
Concurrent Cohort
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place