Open-label randomized trial of titrated disease management for patients with hypertension: Study design and baseline sample characteristics

Abstract

Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥ 140 mm Hg for non-diabetic or ≥ 130 mm Hg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12 months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5 years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6 mm Hg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy.

Introduction

Despite its prevalence, associated morbidity and mortality, presence of evidence-based guidelines, and availability of > 100 anti-hypertensive medications [1], only approximately half of American adults with hypertension (HTN) have achieved adequate blood pressure (BP) control [2], [3]. Clinical trial results indicate that self-management support is critical to successful management of HTN and other chronic conditions [4], [5], [6], [7], [8]. Results from randomized trials would typically lead decision-makers to implement effective strategies per protocol. However, one size may not fit all. Instead, analogous to titrating medications when BP is above clinical targets [9], patients might reasonably require differing intensity of disease management depending on whether they have achieved these clinical targets. We are conducting a pragmatic clinical trial to evaluate the effectiveness of titrated disease management in which the intensity of disease management is adjusted based on an individual's systolic blood pressure (SBP).

We view the process of TDM as analogous to the common process of titrating medication dosage in clinical care. For example, clinical guidelines often recommend adjusting the dosage and/or number of anti-hypertensive agents based on clinical parameters. This is often in the form of stepped care, where patient's initial medication dose is low to minimize risks of treatment (such as side effects) [10]. If patients are not responsive to initial treatments, their medication regimen is intensified until clinical goals are met. Absent some change in the underlying pathophysiology of disease (e.g., weight loss) or side effects, patients do not have their treatment reduced once clinical goals are reached; it is assumed that any reduction in intensity would diminish level of control [11], [12], [13].

We are conducting a pragmatic trial to examine the effectiveness of titrated (not stepped) care when applied to disease management. Specifically, we are adjusting (titrating) the resource intensity (and expense) of a disease management strategy based upon the patient's clinical status. Depending on the individual's BP, resources are either intensified or reduced to achieve or maintain BP control. This resource intensity differs by: 1) who delivers disease management; 2) the complexity of the treatment (i.e., whether there is medication intensification); and 3) frequency of patient contacts. The assumption of this novel approach is that patients will be titrated to different initial resource levels and will be evaluated over time to determine if they will: 1) remain at the same level of resource intensity; 2) increase to a higher intensity level; or 3) decrease to a lower resource intensity level. This type of titration addresses a criticism about stepped care where there is no plan to reduce level of drug or other resource use for patients with improving illness severity [14].