Fixed vs Free Dose of ACEi/CCB Combination Therapy

Hypertension Clinical Trial

— FixFree  

Official title:

Blood Pressure Reduction by Fixed-dose Compared to Free Dose Combination Therapy of ACE Inhibitor and Calcium Antagonist in Hypertensive Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02995954
• Other study ID #: iacca001
• Status: Completed
• Phase: Phase 4
• First received: December 13, 2016
• Last updated: December 16, 2016
• Start date: January 2014
• Est. completion date: December 2015

Study information

• Verified date: December 2016
• Source: Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 80 Years

Eligibility

Inclusion Criteria:

• Hypertensive patients with the first diagnosis of arterial hypertension and in the absence of a previous treatment.

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Perindopril/Amlodipine
Single table containing Perindopril/Amlodipine

Locations

Country	Name	City	State
Italy	San Giovanni e Ruggi Hospital	Salerno

Sponsors (1)

Lead Sponsor	Collaborator
Guido Iaccarino

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	systolic Blood pressure control	reduction in mmHg	3 months	No
Primary	Diastolic Blood pressure control	reduction in mmHg	3 months	No
Secondary	blood pressure control	percentage of patients with BP control	3 months	No