Design/Method This was a single arm, prospective, randomized, single blinded, open label
cross-over study of the urine albumin excretion during the day and at night after 12 weeks of
therapy with either perindopril 8 mg per day or ramipril 10 mg per day in people with
diabetes. Men and women were eligible for the study if they met the following criteria:
Age>18 years, type 2 diabetes with adequate blood sugar control (Hemoglobin A1c (A1c)<8.4%),
therapy with ace inhibitor(ACEi) or angiotensin receptor blocker (ARB) for a period of 8
weeks prior to and throughout the screening period along with blood pressure (BP) <130/80
mmHg, known abnormal albuminuria for at least 12 weeks before screening and throughout the
screening period as defined as (urine albumin by albumin-creatinine ratio (ACR) > 5.0 for men
and women up to 50 mg/mmol).
Exclusion criteria included: women who were pregnant or lactating, women of childbearing age
not on contraception, dual therapy with both ARB and ACEi, 8 weeks prior to screening visit
or during screening period, allergy or history of cough with ACEi, known hypersensitivity to
study medication diluent or to any constituent of study medication, poorly controlled
hypertension (HTN) requiring a change of dose of ACEi or ARB within 8 weeks of screening
visit, change in urine albumin by ≥ 2x from a previous level to the screening level while on
stable drug dosing, myocardial infarction within 12 weeks of screening, congestive heart
failure (NYHA Class IV), severe coronary artery disease, severe liver disease, renal artery
stenosis.
Patients meeting the inclusion and exclusion criteria were enrolled in the study and
randomized. Following this, eligible patients were switched from their existing renin
angiotensin aldosterone system (RAAS) blocker to ramipril 10 mg daily for 1 week to determine
if ramipril was tolerated. They then were entered into a stabilization phase of 12 weeks of
uninterrupted ramipril therapy. Patients were assigned to receive either perindopril 8 mg
once daily or 10 mg ramipril once daily based on the randomization code in an open label
fashion. Treatment with either therapy was for 12 weeks each. At the end of these treatment
periods patients were instructed to collect three sets of spot urine samples to reflect night
and day urine albumin excretion. Additionally, patients were instructed to take four home
blood pressure measurements, 2 in the morning and 2 in the evening. The morning recordings
were to be done before the medication was taken. At the end of the 12 week treatment periods,
measurements of urine electrolytes, A1c, urea, creatinine were also collected. A 24 hour
ambulatory blood pressure monitoring (ABPM) was also completed at the end of the last two
treatment periods.
Laboratory Procedures:
Ambulatory blood pressure was measured was performed over a period of 24 hours using a
clinically validated device (model 90270, Spacelabs Medical Inc., Redmond, Washington, USA).
The machine was instructed to measure blood pressure every 15 minutes throughout the day
(7:00am to 11:00 PM) and every 30 minutes between 11:00pm and 7:00am. Patients were
instructed to remain motionless every time the device was active. Values obtained were
averaged each hour before calculating the day, night and average 24hr blood pressure.
During the 12th week of each treatment period, urine was collected from each patient to
quantitatively measure urine sodium, potassium, urea, creatinine. AER was measured from urine
collected under standard conditions. Three specimens were collected in each treatment period
and the results were analyzed by immunoassay.
Statistical Analysis:
Statistical analysis of data was performed by means of SAS statistical software for Windows
(SAS., Cary, North Carolina) with results being expressed as mean (SD).