Fixed vs Free Dose of ACEi/CCB Combination Therapy
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      The introduction of fixed combination of ACEi+CCB (Fixed) has significantly increased
      patients compliance and adherence to therapy. At the moment, however, there are no data
      suggesting the better control of once-daily fixed (Fixed) over free doses in separate
      administrations combination therapy in hypertensives.

      In a population of 39 consecutive outpatient patients referred to the departmental
      Hypertension clinic of the University Hospital of Salerno Medical School with the first
      diagnosis of arterial hypertension, the investigators tested the hypothesis that the Fixed
      achieve a better control of blood pressure than the Free combination. Patients were
      randomized to either strategy and after 3 months patients underwent a clinical assessment to
      evaluate the antihypertensive effect.
    

Detailed description: 
      Study Population

      Our study included 100 patients referred to the Hypertension Clinic of Salerno Medical School
      Hospital in Salerno, with the first diagnosis of arterial hypertension and in the absence of
      a previous treatment. At the time of enrollment visit, patients signed a consent to anonymous
      participation, in compliance with the regulations of good clinical practice and privacy.
      Study participants were 18-75 years old with essential hypertension (defined according to the
      ESH / ESC 2013 guidelines). Patients were excluded if patients had secondary hypertension,
      malignant hypertension, CRF (chronic renal failure), oncological conditions or cirrhosis.
      Patients were also excluded if patients had medical and surgical disorders that alter
      absorption, distribution, metabolism and excretion of drug treatment. The study protocol was
      approved by the competent University Hospital Ethical Committee.

      Study Design

      Patients were randomized to either fixed dose or free dose combination therapy, with
      Perindopril (5 or 10 mg) and Amlodipine (5 or 10 mg) with a 2:1 randomization design based on
      a power analysis. Doses were decided according to anthropometric, clinical, biochemical and
      instrumental doses by experienced medical staff. The Fixed group received one single tablet
      containing Perindopril/Amlodipine at the appropriate dose. The Free group, received
      Perindopril and Amlodipine in separate tablets at the appropriate dose. Groups were matched
      for age, sex, BMI, systolic BP (SBP) and diastolic BP (DBP). At baseline and at follow-up the
      investigators evaluated clinical (weight, height, BMI, heart rate, BP) and biochemical
      parameters (blood glucose, serum cholesterol, LDL, HDL, triglycerides, blood urea nitrogen,
      creatinine, creatinine clearance), as well as Electrocardiogram (ECG) and cardiac ultrasound.

      Clinical parameters

      In accordance with the ESH guidelines, BP assessment was carried out noting two measurements
      in the supine, in sitting and in standing position, spaced apart from 1-2 minutes. For the
      current study mean values in sitting position were considered. BP measurements were assessed
      by trained personnel using a dedicated, upper arm, electronic machine (Afib screen,
      Microlife, Italy) Anthropometric parameters.

      The weight classes were defined by BMI [weight (kg)/height (m)2]. In adults, overweight is
      identified by a BMI of 25-29.9 kg/m2, and obesity by a BMI≥30 kg/m2.

      Biochemical parameters

      For each patient, the following laboratory tests were evaluated: fasting glucose, total
      cholesterol, LDL, HDL, triglycerides, blood urea nitrogen (BUN), serum creatinine and
      creatinine clearance (calculated with MDRD or Cockroft formula).

      Fasting blood glucose greater than 126 mg/dl was used for screening for diabetes.

      Follow-up with computerized medical records

      The patient population was included in a central database that uses Wincare software
      (TSD-Projects, Milan, Italy), which contains separate electronic sheets for medical history,
      physical examination, laboratory tests, electrocardiogram, cardiac ultrasounds, other imaging
      tests and ambulatory blood pressure monitoring. The data was updated at each follow-up visit
      with a revaluation deadline set at three months. The data of each patient are stored on the
      hospital server and protected by a firewall system with password access.

      Echocardiography

      All patients were subjected to one-dimensional echocardiography (M-mode), two-dimensional
      (B-mode) and Doppler function via the 5-1MHz probe (E9, GE Healthcare).

      Statistical analysis

      Categorical data are presented as percent while continuous data are indicated as means ±
      standard error. The quantitative analysis was performed using T-test for unpaired data or
      ANOVA as appropriate, while the qualitative analysis was performed using non-parametric tests
      (χ2 test). A value of p-value <0.05 was considered statistically significant. All data were
      analyzed using Prism 6.0 (GraphPad Software, Inc., San Diego, CA).
    

Intervention name(s): Perindopril/Amlodipine
Intervention type(s): Drug
Intervention description(s): Single table containing Perindopril/Amlodipine
Other intervention name(s): Perindopril amlodipine
Intervention MeSH terms: Amlodipine; Perindopril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Combination therapy; ACE inhibitor Calcium Antagonist