EBMtrialcentral- Comparing Initial Diuretic Therapies Using a Collaborative Network

- BACKGROUND:

The application of many traditional randomized controlled trial(RCT) findings to real-world
practice is in question. To this end, comparative effectiveness research(CER) has evolved.
However, there remains ample evidence that U.S. trials are becoming increasingly cumbersome
and expensive. Moreover, 90 percent fail to meet enrollment goals.

In contrast, there have been significant recent technological advances in both
bioinformatics and social media. However, thus-far, the combined potential of both has yet
to be achieved in the field of medicine. The stage is now set for an amalgamation of these
three disciplines; CER, bioinformatics and social media. EBMtrialcentral is a non-profit
website developed at Johns Hopkins University with the idea of using an online social
network to actually perform CER trials. By harnessing the power of social media,
EBMtrialcentral could open up a world of opportunity for conducting clinical research and
bring randomization into "usual care".

- OBJECTIVES:

1. To determine if a social network website can be created, among a group of academic
physicians, with the pre-specified objective of using this website to conduct a
CER trial.

2. To perform a pilot-study though the website. This study will randomly allocate
initial anti-hypertensive treatment strategies, using guideline recommended
diuretic agents.

- METHODS:

1. Website development-A test website, EBMtrialcentral.org, has been initiated. By
visiting the website, eligible physicians will be able to join the collaborative
network. Once a member physician identifies an eligible patient who agrees to
participate, consent forms will be generated online for formal enrollment. A
therapeutic strategy will be randomly allocated via the website. The
investigators' platform would require parsimonious imputation of secured patient
data. Follow-up will be pragmatic and guideline-directed. Data will initially be
managed in a protected online database run by "project REDCap". Patients and
patient advocate stakeholders will be invited to help with IRB and website
development.

2. Pilot study-Despite stronger evidence for chlorthalidone, most hypertensive
patients prescribed diuretics currently receive HCTZ. However, the two have not
been randomly compared in an adequately powered study. The investigators will
require 80 newly hypertensive urban subjects to detect a greater than 5mmHg mean
automated BP difference between the two groups over 2 monthly follow-up visits (8
weeks total, with a standardized effect size of 0.7 based on prior data). The
investigators will include ethnic and under-served subjects. Exclusion criteria
will include compelling indications for alternative anti-hypertensives.
Non-blinded random allocation will be generated online.

Inclusion Criteria:

- Men and women are eligible if they have hypertension, are not receiving
antihypertensive medications, and have average office BP values within the last 6
months ≥140/90 mmHg.

Exclusion Criteria:

- Patients with hypertensive urgency will be excluded (BP ≥180/120 mmHg). We also plan
to exclude those with "compelling indications" for an ACE inhibitor or Beta-blocker
therapy (per JNC 7). These include those with; a history of diabetes (prior HbA1c
≥6.5%, fasting glucose ≥126mg/dl, a history of insulin or oral hypoglycemic use, or
microalbuminuria), myocardial infarction within the last 3 years, and a known LVEF
<50%. Other safety exclusions will be; a history of chronic kidney disease (or a
serum creatinine ≥1.8 mg/dL), known allergy to study medications, inability to
provide consent, a history of significant non-compliance or missed appointments, a
history of poorly-controlled gout and a history of falls or autonomic dysfunction and
subjects aged <21years or ≥90yrs.