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

This study has been completed.
Sponsor:
Collaborator:
Kaiser Permanente
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01078246
First received: February 26, 2010
Last updated: March 9, 2016
Last verified: March 2016
  Purpose
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.

Condition
HIV-1 Infections

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Post-Licensure Safety Study of ISENTRESS™ in a US Managed Care Network

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Incidence of AIDS-defining and Non-AIDS-defining Malignancy [ Time Frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of Clinically Important Hepatic Events [ Time Frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of Clinically Important Skin Events [ Time Frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of Clinically Important Muscle Events [ Time Frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of Lipodystrophy [ Time Frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Incidence of Clinically Important Cardiovascular Events [ Time Frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of All-cause Mortality [ Time Frame: Historical Cohort: up to 33 months (January 2005 to October 2007); Raltegravir and Concurrent Cohorts: up to 69 months (October 2007 to June 2013) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 7124
Study Start Date: August 2009
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

Detailed Description:
Study participants contributed data to one or more of 3 cohorts: 1) Historical Cohort: HIV-infected participants treated with antiretroviral therapy in the course of ordinary clinical practice at the clinics and medical centers of Kaiser Permanente (KP) between 1 January 2000 and 12 October 2007 (date of market authorization for raltegravir in USA), 2) Concurrent Cohort: HIV-infected participant treated with a new non-raltegravir antiretroviral therapy in the course of ordinary clinical practice at the clinics and medical centers of KP on or after 12 October 2007, and 3) Raltegravir Cohort: HIV-infected participant treated with raltegravir in the course of ordinary clinical practice at the clinics and medical centers of KP on or after 12 October 2007. Participants could contribute data to more than one cohort, but no overlap in follow-up time was allowed.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adults 18 years old and older
Criteria

Inclusion Criteria:

  • Historical Cohort: HIV-infected participant treated with antiretroviral therapy in the course of ordinary clinical practice at the clinics and medical centers of Kaiser Permanente (KP) between 1 January 2000 and 12 October 2007 (date of market authorization for raltegravir in USA)
  • Raltegravir Cohort: HIV-infected participant treated with raltegravir in the course of ordinary clinical practice at the clinics and medical centers of KP on or after 12 October 2007
  • Concurrent Cohort: HIV-infected participant treated with a new non-raltegravir antiretroviral therapy in the course of ordinary clinical practice at the clinics and medical centers of KP on or after 12 October 2007
  • All participants must have at least one year of continuous membership with KP prior to date when the participant received the first dispensed prescription for study drug (index date) to allow for the assessment of medical and treatment history

Exclusion Criteria:

  • Less than 18 years of age
  • Do not receive their medications through the KP pharmacy system
  • Do not receive their laboratory examinations through the KP system
  • Participating in the raltegravir phase III or expanded access program
  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: NCT01078246

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Kaiser Permanente
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01078246     History of Changes
Other Study ID Numbers: 0518-268  EP08025.006  2010_021 
Study First Received: February 26, 2010
Results First Received: March 9, 2016
Last Updated: March 9, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Merck Sharp & Dohme Corp.:
HIV

Additional relevant MeSH terms:
Raltegravir Potassium
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2016