N-of-1 Trials for Blood Pressure Medications in Adults

The goal of this research is to empower hypertensive patients to learn which blood pressure
(BP) medication is best for them. Although lifestyle factors such as diet and exercise play
an important role, medications may still needed to achieve BP control. Yet, there are
substantial differences in the way BP medications affect patients; medications well-tolerated
in some, cause severe side-effects in others. Similarly, medications that cause larger
reductions in BP in some patients have smaller BP lowering effects in others. Despite this
heterogeneity in treatment effects, there are no proven real-world methods to help patients
identify the medication most suited to their needs.

One potential approach to individualizing BP treatment decisions is to conduct N-of-1 trials:
a multiple crossover design conducted in a single patient. Despite the appeal of this
approach, there are few published reports of BP medication N-of-1 trials. Therefore, the
objective of this study is to determine the feasibility of conducting an N-of-1 BP medication
trial in hypertensive patients. Patients who meet all the eligibility criteria will be asked
to monitor their blood pressure and side-effects while taking a series of commonly prescribed
blood pressure medications. If they are already taking a blood pressure medication, they will
begin by tracking their blood pressure and side-effects while taking this medication for 1
week. They will then be asked to track their blood pressure and side-effects while taking a
series of up to three other blood pressure medications (losartan - a renin-angiotensin system
blocking agent, amlodipine - a calcium channel blocker, and hydrochlorothiazide - a thiazide
diuretic). Each of these medications will be taken for 2 weeks at a time. The specific choice
of medications and medication doses will be selected by the study physician. Unless patients
have side-effects that lead them to discontinue a medication early, patients will be expected
to take each medication at least twice in a balanced sequence (e.g., losartan - amlodipine -
HCTZ - HCTZ - amlodipine - losartan). Patients will measure their blood pressure and
medication side-effects during the 2nd week on each of these medications. Patients will have
the option of escalating or decreasing dosages to identify the single medication/medication
dose that best lowers their blood pressure with the least side-effects. Blood pressure will
be measured using an Omron home blood pressure monitor. Side-effects will be tracked using a
daily e-mailed survey that is completed over the Internet.

Inclusion Criteria:

- Age 21 to 80 years.

- History of physician-diagnosed hypertension.

- Currently not treated with antihypertensive medication but with consensus (from
patient and his/her physician; patients with elevated ABPM who are not on treatment
will be considered eligible irrespective of office BP if the patient's physician is in
agreement with a trial of BP medications) that antihypertensive medication should be
initiated; or being treated with one antihypertensive medication.

- No history of suspected or confirmed white coat hypertension (elevated clinic BP but
non-elevated out-of-clinic BP either by home BP monitoring or ABPM).

- Easy access to and regular use of e-mail as they will need to be able to respond to
Qualtrics surveys at regular intervals during the self-monitoring period.

- Established relationship with an accessible primary care provider.

- Primary care provider gives permission to participation in an N-of-1 trial.

Exclusion Criteria:

- Severe hypertension (office BP = 180/110 mm Hg).

- History of myocardial infarction, heart failure, atrial fibrillation, or chronic
kidney disease as these patients have guideline recommended indications for specific
classes of BP medications.

- Electrolyte abnormality; if no electrolyte panel is available in the prior 6 months,
then one will be ordered for purposes of the study.

- Known drug allergy or intolerance to angiotensin receptor blocker, calcium channel
blocker, or thiazide diuretic.

- Prescribed BP medication for indication other than hypertension (e.g., migraine
headache prophylaxis, enlarged prostate).

- Primary care provider permission not obtained.

- Non-English speaking.

- No regular (daily) access and use of e-mail as participants will need to be able to
respond to emailed links to surveys for completion of self-monitoring symptoms.

- Unable to provide informed consent or adhere to study protocol due to cognitive
impairment, mental illness, or other reasons.

- Unable to monitor BP at home using an automatic BP machine due to physical or mental
impairments.

- Unable to track side effects of medications due to physical or mental impairments
including literacy problems.

- Arm circumference <9 inches or >17 inches as these sizes do not accommodate the range
of BP cuff sizes that are available for the automatic BP machine.

- Unavailable for follow-up during the study period due to severe medical illness or
other reasons.