Case Study 3 -
Treatment of Hypertension: An Open-Label Phase II Clinical Trial

Approximately one quarter of all Canadians have been diagnosed with hypertension (high blood pressure), a major risk factor for heart disease and Canada's leading cause of death. Over time, high blood pressure may lead to heart problems, damage to the kidneys, and stroke. Two out of three people with high blood pressure have conditions that are not well controlled, and many people with high blood pressure receive two or more medications daily. Side effects from blood pressure medications are common.

Researchers designed a clinical trial to test an experimental drug that would enable people to take only one pill, which would control hypertension over a 24-hour period. Men and women 18 years of age and older were recruited for this study. To be eligible, participants needed to have:

• been initially diagnosed through a routine medical assessment with a systolic blood pressure of between 140 mmHg and 180 mmHg and a diastolic pressure of over 90 mmHg to 105 mmHg, and
• taken previous blood pressure medication for at least four weeks and experienced undesirable side effects from it and/or showed no improvement.

The study began with a two-week washout period (that is, time the patient spends off his or her usual medication). This was followed by two to four weeks of single blind treatment to determine the optimum dose, and then a 16-week open-label treatment period. (An open-label study is a drug clinical trial in which both the researchers and the patient know the identity of the test drug.) The total duration of the study could be as long as 22 weeks. Participants monitored their blood pressure at home, kept a daily diary of their blood pressure and any symptoms for 22 weeks, and underwent regular blood tests and further blood pressure checks at the clinic. The study was intended to determine if the new drug taken once daily would control high blood pressure for a 24-hour period without causing undesirable side effects, and, if so, to identify the optimum dose.

Possible risks of the new medication were:

• The patient could experience mild to moderate worsening of hypertension during the washout phase while off his or her usual medication, and mild to moderate dose-range side effects during the adjustment phase. Hypertension could also worsen during the treatment phase.
• These side effects occur occasionally (though they are temporary and gradually go away once the treatment is stopped): headache, fatigue, infection, nausea, diarrhea, chest pain, sore throat, thirst, increased urinary frequency, acid indigestion, dizziness and sleepiness. Mild to moderate laboratory abnormalities could occur, including decreased potassium levels.
• Blood drawing could cause mild discomfort, bruising, bleeding, swelling, and/or light-headedness.

Study subjects were asked to contact the blood pressure clinic if their systolic blood pressure was higher than 180 mmHg or if they experienced any of the side effects from the study medication.