<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02995954</url>
  </required_header>
  <id_info>
    <org_study_id>iacca001</org_study_id>
    <nct_id>NCT02995954</nct_id>
  </id_info>
  <brief_title>Fixed vs Free Dose of ACEi/CCB Combination Therapy</brief_title>
  <acronym>FixFree</acronym>
  <official_title>Blood Pressure Reduction by Fixed-dose Compared to Free Dose Combination Therapy of ACE Inhibitor and Calcium Antagonist in Hypertensive Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guido Iaccarino</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The introduction of fixed combination of ACEi+CCB (Fixed) has significantly increased&#xD;
      patients compliance and adherence to therapy. At the moment, however, there are no data&#xD;
      suggesting the better control of once-daily fixed (Fixed) over free doses in separate&#xD;
      administrations combination therapy in hypertensives.&#xD;
&#xD;
      In a population of 39 consecutive outpatient patients referred to the departmental&#xD;
      Hypertension clinic of the University Hospital of Salerno Medical School with the first&#xD;
      diagnosis of arterial hypertension, the investigators tested the hypothesis that the Fixed&#xD;
      achieve a better control of blood pressure than the Free combination. Patients were&#xD;
      randomized to either strategy and after 3 months patients underwent a clinical assessment to&#xD;
      evaluate the antihypertensive effect.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Population&#xD;
&#xD;
      Our study included 100 patients referred to the Hypertension Clinic of Salerno Medical School&#xD;
      Hospital in Salerno, with the first diagnosis of arterial hypertension and in the absence of&#xD;
      a previous treatment. At the time of enrollment visit, patients signed a consent to anonymous&#xD;
      participation, in compliance with the regulations of good clinical practice and privacy.&#xD;
      Study participants were 18-75 years old with essential hypertension (defined according to the&#xD;
      ESH / ESC 2013 guidelines). Patients were excluded if patients had secondary hypertension,&#xD;
      malignant hypertension, CRF (chronic renal failure), oncological conditions or cirrhosis.&#xD;
      Patients were also excluded if patients had medical and surgical disorders that alter&#xD;
      absorption, distribution, metabolism and excretion of drug treatment. The study protocol was&#xD;
      approved by the competent University Hospital Ethical Committee.&#xD;
&#xD;
      Study Design&#xD;
&#xD;
      Patients were randomized to either fixed dose or free dose combination therapy, with&#xD;
      Perindopril (5 or 10 mg) and Amlodipine (5 or 10 mg) with a 2:1 randomization design based on&#xD;
      a power analysis. Doses were decided according to anthropometric, clinical, biochemical and&#xD;
      instrumental doses by experienced medical staff. The Fixed group received one single tablet&#xD;
      containing Perindopril/Amlodipine at the appropriate dose. The Free group, received&#xD;
      Perindopril and Amlodipine in separate tablets at the appropriate dose. Groups were matched&#xD;
      for age, sex, BMI, systolic BP (SBP) and diastolic BP (DBP). At baseline and at follow-up the&#xD;
      investigators evaluated clinical (weight, height, BMI, heart rate, BP) and biochemical&#xD;
      parameters (blood glucose, serum cholesterol, LDL, HDL, triglycerides, blood urea nitrogen,&#xD;
      creatinine, creatinine clearance), as well as Electrocardiogram (ECG) and cardiac ultrasound.&#xD;
&#xD;
      Clinical parameters&#xD;
&#xD;
      In accordance with the ESH guidelines, BP assessment was carried out noting two measurements&#xD;
      in the supine, in sitting and in standing position, spaced apart from 1-2 minutes. For the&#xD;
      current study mean values in sitting position were considered. BP measurements were assessed&#xD;
      by trained personnel using a dedicated, upper arm, electronic machine (Afib screen,&#xD;
      Microlife, Italy) Anthropometric parameters.&#xD;
&#xD;
      The weight classes were defined by BMI [weight (kg)/height (m)2]. In adults, overweight is&#xD;
      identified by a BMI of 25-29.9 kg/m2, and obesity by a BMI≥30 kg/m2.&#xD;
&#xD;
      Biochemical parameters&#xD;
&#xD;
      For each patient, the following laboratory tests were evaluated: fasting glucose, total&#xD;
      cholesterol, LDL, HDL, triglycerides, blood urea nitrogen (BUN), serum creatinine and&#xD;
      creatinine clearance (calculated with MDRD or Cockroft formula).&#xD;
&#xD;
      Fasting blood glucose greater than 126 mg/dl was used for screening for diabetes.&#xD;
&#xD;
      Follow-up with computerized medical records&#xD;
&#xD;
      The patient population was included in a central database that uses Wincare software&#xD;
      (TSD-Projects, Milan, Italy), which contains separate electronic sheets for medical history,&#xD;
      physical examination, laboratory tests, electrocardiogram, cardiac ultrasounds, other imaging&#xD;
      tests and ambulatory blood pressure monitoring. The data was updated at each follow-up visit&#xD;
      with a revaluation deadline set at three months. The data of each patient are stored on the&#xD;
      hospital server and protected by a firewall system with password access.&#xD;
&#xD;
      Echocardiography&#xD;
&#xD;
      All patients were subjected to one-dimensional echocardiography (M-mode), two-dimensional&#xD;
      (B-mode) and Doppler function via the 5-1MHz probe (E9, GE Healthcare).&#xD;
&#xD;
      Statistical analysis&#xD;
&#xD;
      Categorical data are presented as percent while continuous data are indicated as means ±&#xD;
      standard error. The quantitative analysis was performed using T-test for unpaired data or&#xD;
      ANOVA as appropriate, while the qualitative analysis was performed using non-parametric tests&#xD;
      (χ2 test). A value of p-value &lt;0.05 was considered statistically significant. All data were&#xD;
      analyzed using Prism 6.0 (GraphPad Software, Inc., San Diego, CA).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>systolic Blood pressure control</measure>
    <time_frame>3 months</time_frame>
    <description>reduction in mmHg</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Diastolic Blood pressure control</measure>
    <time_frame>3 months</time_frame>
    <description>reduction in mmHg</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>blood pressure control</measure>
    <time_frame>3 months</time_frame>
    <description>percentage of patients with BP control</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Fixed</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The Fixed group received one single tablet containing Perindopril/Amlodipine (Reaptan) at the appropriate dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Free</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The Free group, received Perindopril and Amlodipine in separate tablets at the appropriate dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perindopril/Amlodipine</intervention_name>
    <description>Single table containing Perindopril/Amlodipine</description>
    <arm_group_label>Fixed</arm_group_label>
    <arm_group_label>Free</arm_group_label>
    <other_name>Perindopril amlodipine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hypertensive patients with the first diagnosis of arterial hypertension and in the&#xD;
             absence of a previous treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients were excluded if patients had secondary hypertension, malignant hypertension,&#xD;
             CRF (chronic renal failure), oncological conditions or cirrhosis.&#xD;
&#xD;
          -  Patients were also excluded if patients had medical and surgical disorders that alter&#xD;
             absorption, distribution, metabolism and excretion of drug treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>San Giovanni e Ruggi Hospital</name>
      <address>
        <city>Salerno</city>
        <zip>84100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <last_update_submitted>December 16, 2016</last_update_submitted>
  <last_update_submitted_qc>December 16, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona</investigator_affiliation>
    <investigator_full_name>Guido Iaccarino</investigator_full_name>
    <investigator_title>Associate Professor of Internal of Medicine</investigator_title>
  </responsible_party>
  <keyword>Combination therapy</keyword>
  <keyword>ACE inhibitor Calcium Antagonist</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amlodipine</mesh_term>
    <mesh_term>Perindopril</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02995954
org study id: iacca001
nct id: NCT02995954
lead sponsor: 
has dmc: No
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.
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: systolic Blood pressure control
time frame: 3 months
description: reduction in mmHg
measure: Diastolic Blood pressure control
time frame: 3 months
description: reduction in mmHg
measure: blood pressure control
time frame: 3 months
description: percentage of patients with BP control
arm group label: Fixed
arm group type: Active Comparator
description: The Fixed group received one single tablet containing Perindopril/Amlodipine (Reaptan) at the appropriate dose
arm group label: Free
arm group type: Active Comparator
description: The Free group, received Perindopril and Amlodipine in separate tablets at the appropriate dose
intervention type: Drug
intervention name: Perindopril/Amlodipine
description: Single table containing Perindopril/Amlodipine
arm group label: Fixed
arm group label: Free
other name: Perindopril amlodipine
criteria: 
gender: All
minimum age: 35 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Italy
responsible party type: Sponsor-Investigator
investigator affiliation: Azienda Ospedaliera OO.RR. S. Giovanni di Dio e Ruggi D'Aragona
investigator full name: Guido Iaccarino
investigator title: Associate Professor of Internal of Medicine
mesh term: Hypertension
mesh term: Amlodipine
mesh term: Perindopril
sharing ipd: No