NCT01078246

Post-Licensure Safety Study of ISENTRESS™ (Raltegravir) in a United States Managed Care Network (MK-0518-268)

Completed Results posted Last updated 22 August 2018

What this trial tests

trial in HIV-1 Infections in 7,124 participants. Completed in 9 December 2014.

Timeline

31 August 2009

Primary endpoint
9 December 2014

9 December 2014

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Status	Completed
Study type	OBSERVATIONAL
Enrollment	7,124
Start date	31 August 2009
Primary completion	9 December 2014
Estimated completion	9 December 2014

Conditions studied

• HIV-1 Infections — all drugs for HIV-1 Infections →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with HIV-1 Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Incidence of AIDS-defining and Non-AIDS-defining Malignancy Primary · Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)

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 lymphom

AIDS-defining Malignancy

Group	Value	95% CI
Raltegravir Cohort	13.0	9.6 – 16.3
Historical Cohort	8.9	5.7 – 12.2
Concurrent Cohort	9.3	7.4 – 11.2

Non-AIDS-defining Malignancy

Group	Value	95% CI
Raltegravir Cohort	18.2	14.3 – 22.1
Historical Cohort	9.1	5.8 – 12.3
Concurrent Cohort	10.3	8.3 – 12.3

Incidence of Clinically Important Hepatic Events Primary · Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)

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.

Group	Value	95% CI
Raltegravir Cohort	19.0	14.9 – 23.0
Historical Cohort	25.0	19.6 – 30.5
Concurrent Cohort	17.1	14.5 – 19.7

Incidence of Clinically Important Skin Events Primary · Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)

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.

Group	Value	95% CI
Raltegravir Cohort	40.6	34.4 – 46.8
Historical Cohort	69.8	60.4 – 79.2
Concurrent Cohort	63.6	58.2 – 69.1

Incidence of Clinically Important Muscle Events Primary · Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)

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.

Group	Value	95% CI
Raltegravir Cohort	3.4	1.7 – 5.1
Historical Cohort	3.3	1.4 – 5.3
Concurrent Cohort	1.5	0.7 – 2.3

Incidence of Lipodystrophy Primary · Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)

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 repor

Group	Value	95% CI
Raltegravir Cohort	20.6	15.9 – 25.4
Historical Cohort	35.6	28.9 – 42.4
Concurrent Cohort	9.2	7.2 – 11.1

Incidence of Clinically Important Cardiovascular Events Secondary · Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)

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. In

Group	Value	95% CI
Raltegravir Cohort	6.7	4.4 – 9.1
Historical Cohort	6.4	3.7 – 9.1
Concurrent Cohort	4.0	2.8 – 5.3

Incidence of All-cause Mortality Secondary · Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013)

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.

Group	Value	95% CI
Raltegravir Cohort	16.9	13.3 – 20.6
Historical Cohort	18.4	13.7 – 23.0
Concurrent Cohort	7.7	6.0 – 9.4

Sponsor's own description

The objective of this study is to monitor Health Outcomes of Interest (HOI) in participants with human immunodeficiency virus-1 (HIV-1) infection following treatment with Raltegravir.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.