Fixed Dose Intervention Trial of New England Enhancing Survival in SMI Patients
Condition: Serious Mental Illness; Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Cardiovascular Disease; Major Depressive Disorder; Psychosis NOS
MeSH terms: Cardiovascular Diseases; Schizophrenia; Depressive Disorder; Depressive Disorder, Major; Bipolar Disorder; Psychotic Disorders; Mental Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients with severe mental illness (SMI) die younger than persons in the general population.
      Much of the excess mortality for SMI patients is attributable to cardiovascular disease, and
      is exacerbated by treatment with second-generation antipsychotics (2GAs). Although the
      cardiovascular risks are well-known, and safe, efficacious therapy exists, few SMI patients
      receive cardiovascular prevention drugs. Care delivery fragmentation and poor patient
      adherence are central problems to reducing cardiovascular risks for patients with SMI. To
      address these problems, we propose to conduct a multi-site, open-label, randomized controlled
      trial comparing an initial treatment strategy of free, fixed-doses of two generic,
      cardiovascular prevention drugs (statins and angiotensin drugs) delivered within mental
      health clinics versus usual treatment. The study will include adult patients (18+ years old)
      with schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder, or
      psychosis not otherwise specified (NOS) who have received 2GAs treatment within the past six
      months from within four mental health clinics in the Boston area. We have three aims: 1) to
      compare the proportions of subjects in each arm who are receiving cardiovascular drug
      treatment and are adherent to therapy during 12-months of follow-up; 2) to compare changes in
      composite (e.g., Framingham scores) and individual (e.g., lipid levels) cardiovascular risk
      factor levels using an intent-to-treat (ITT) approach; and 3) to compare risk factor levels,
      accounting for variation in adherence over time, using causal inference techniques to
      estimate the per-protocol effect of the intervention. Our three aims examine whether this low
      cost, streamlined treatment strategy increases the numbers of subjects receiving
      cardiovascular prevention therapy and improves cardiovascular risk levels. We will follow
      subjects for 12 months, and collect interview and biometric data at baseline and over the
      following 12 months. Subjects will have the option to continue for another 12 months, during
      which we will continue to collect interview and biometric data, but will not prescribe
      cardiovascular medications. This population-based initial treatment strategy could be an
      effective and efficient approach for overcoming traditional barriers to cardiovascular
      disease prevention within the SMI population. Findings from this study will inform efforts to
      improve care and outcomes, and to enhance survival for patients with severe mental illness.
    

Detailed description: 
      By design, all subjects in the Intervention arm will start by being under treatment. During
      the course of follow-up, we expect that some will stay consistently on treatment, some will
      discontinue treatment (become non-adherent), while others will make transitions on and off
      treatment in various patterns. In contrast, by design, subjects in the Usual Treatment
      (control) arm do not start on treatment; however, some will initiate treatment as a result of
      usual clinical care, e.g., primary care physician initiation. At any point we will be
      comparing two binary outcomes (on or off treatment) and will use standard methods for
      comparing two proportions to test statistical significance and get confidence intervals for
      the difference in the percent on treatment in the two arms. Participants who are ineligible
      for randomization will be followed similarly to participants in the Usual Treatment Arm, in a
      third, non-randomized group, which will be excluded from the primary analysis.
    

Intervention name(s): Simvastatin; Losartan
Intervention type(s): Drug; Drug
Intervention description(s): 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors; Angiotensin II receptor antagonist
Intervention MeSH terms: Losartan; Simvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment