Efficacy/Safety Study of Valsartan and Chlorthalidone Conjugate Treatment Compared to Simple Treatment for Hypertension

• ClinicalTrials.gov Identifier: NCT01850160
• Recruitment Status: Completed
• First Posted: May 9, 2013
• Last Update Posted: January 26, 2016
• Sponsor: Farma de Colombia SA
• Information provided by (Responsible Party): Farma de Colombia SA

Tracking Information

• First Submitted Date: May 7, 2013
• First Posted Date: May 9, 2013
• Last Update Posted Date: January 26, 2016
• Study Start Date: April 2013
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2013)

Safety and Efficacy of the fixed-dose combination treatment with Valsartan plus Chlorthalidone [ Time Frame: 12 weeks ]

Efficacy and safety of a fixed-dose combination treatment of Valsartan plus Chlorthalidone Vs Valsartan or Chlorthalidone alone in the treatment of patients with arterial hypertension

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 9, 2013)

• Changes in Systolic and Diastolic Blood pressure values [ Time Frame: 12 weeks ]
  Assess the changes in Systolic and Diastolic Blood Pressure from baseline up to week 12
• Changes of Systolic blood pressure values [ Time Frame: 12 weeks ]
  Assess the changes of systolic blood pressure from baseline up to week 6 and 12
• Changes of Diastolic blood pressure values [ Time Frame: 12 weeks ]
  Assess the changes of diastolic blood pressure from baseline up to week 6 and 12
• Changes of diastolic blood pressure in arterial blood pressure median values [ Time Frame: 12 weeks ]
  Assess the changes in diastolic blood pressure in Arterial Blood Pressure Media from baseline up to week 12
• Changes of systolic blood pressure values in arterial blood pressure median values [ Time Frame: 12 weeks ]
  Assess the change in systolic blood pressure in Arterial Blood Pressure Median from baseline up to week 12
• Patient that achieving blood pressure values lower than 140/90 (systolic/diastolic) at week 6 and 12 [ Time Frame: 12 weeks ]
  Determine the percentage of patients achieving blood pressure values lower than 140/90 (systolic/diastolic) at weeks 6 and 12
• Patients that achieving systolic blood pressure values lower than 140 at week 6 and 12 [ Time Frame: 12 weeks ]
  Determine the percentage of patients achieving systolic blood pressure lower than 140 at weeks 6 and 12
• Patients that achieving diastolic blood pressure values lower than 90 at week 6 and 12 [ Time Frame: 12 weeks ]
  Determine the percentage of patients achieving diastolic blood pressure lower than 90 at week 6 and 12

Original Secondary Outcome Measures (submitted: May 7, 2013)

Changes in Systolic and Diastolic Blood pressure [ Time Frame: 12 weeks ]

Changes in Systolic and Diastolic Blood Pressure from baseline up to week 12

Current Other Pre-specified Outcome Measures (submitted: May 9, 2013)

• Metabolic changes secondary to the treatment with Valsartan and Chlorthalidone, Vs Valsartan or Chlorthalidone [ Time Frame: 12 weeks ]
  Identify if there are significant differences regarding metabolic changes secondary to the treatment with Valsartan and Chlorthalidone Vs Valsartan or Chlorthalidone.
• Incidence of adverse events in each intervention group [ Time Frame: 12 weeks ]
  Determine the percentage of incidence of adverse events in each intervention group.

Original Other Pre-specified Outcome Measures (submitted: May 7, 2013)

• Change of Systolic blood pressure [ Time Frame: 12 weeks ]
  Change in systolic blood pressure from baseline up to week 6 and 12
• Change of Diastolic blood pressure [ Time Frame: 12 weeks ]
  Change in diastolic blood pressure from baseline up to week 6 and 12
• Patients with systolic blood Pressure lower than 140 mmHg [ Time Frame: 12 weeks ]
  Determinate the percentage of patients achieving Systolic blood pressure lower than 140 mmHg at week 6 and 12
• Patients with Diastolic blood pressure lower than 90 mmHg [ Time Frame: 12 weeks ]
  Determinate the percentage of patients achieving Diastolic blood pressure lower than 90 mmHg at week 6 and 12
• Metabolic changes secondary to the treatment [ Time Frame: 12 weeks ]
  Measure the significant differences related with metabolic changes secondary to the treatment with Valsartan and Chlorthalidone Vs Valsartan or Chlorthalidone
• Incidence rate of adverse events [ Time Frame: 12 weeks ]
  Determinate the incidence events in each intervention group

Descriptive Information

• Brief Title: Efficacy/Safety Study of Valsartan and Chlorthalidone Conjugate Treatment Compared to Simple Treatment for Hypertension
• Official Title: Efficacy and Safety of the Fixed-dose Combination of Valsartan Plus Chlorthalidone Vs Valsartan or Chlorthalidone Alone in the Treatment of Arterial Hypertension, Open-label, Controlled, Randomized and Multicenter Trial
• Brief Summary: This trial is aimed to assess the efficacy and safety of a fixed-dose combination therapy with Valsartan and Chlorthalidone, Vs Valsartan or Chlorthalidone alone for treatment of adult patients with diagnosis of arterial hypertension.

Detailed Description

In spite of the existence of a great variety of treatments with drugs effective against arterial hypertension, the percentages of arterial hypertension control with monotherapy remain quite low reason why the fixed-dose combinations of drugs have been one of the most interesting research topics in order to achieve an appropriate control of arterial hypertension.

The possibility of achieving better coverage and Blood Pressure control through a drug combination has leaded, on a scientific base of the efficacy of an Angiotensin Receptor Blockers II plus diuretic combination, to the development of a great number of combinations with different Angiotensin II Receptor Blockers plus hydrochlorothiazide. Yet it is noteworthy that despite the increasing evidence showing additional benefits in Blood pressure control and reduction of cardiovascular outcomes with chlorthalidone over hydrochlorothiazide, there is neither a great number of combinations nor studies with Angiotensin II Receptor Blockers plus chlorthalidone whereby the conduction of a trial assessing the efficacy and safety of Valsartan plus chlorthalidone in hypertensive patients is proposed plus the benefits of combination therapy that include, among others, the greater efficacy with lower doses of each individual component as well as reduction in occurrence of adverse events directly related with lower drug doses.With this treatment schedule it is expected to obtain higher control of blood pressure values and greater percentage of patients.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hypertension

Intervention

• Drug: GROUP A: Valsartan plus Chlorthalidone
  Combination therapy of Valsartan plus Chlorthalidone: Valsartan 80 mg / Chlorthalidone 12,5 mg. Once daily during 12 weeks. If the goals of blood Pressure are uncontrolled at week 6, the dose will be increase to Valsartan 160 mg / Chlorthalidone 25 mg once daily.
  Other Names:

  • Chlorthalidone Drug Combination
  • Valsartan Drug Combination
  • Antihypertensive Agents
• Drug: GROUP B: Valsartan
  GROUP B: Treatment monotherapy: Valsartan 80 mg once daily during 12 weeks. If the goals of blood Pressure are uncontrolled at week 6, the dose will be increase to Valsartan 160 mg once daily.
  Other Names:

  • Angiotensin II Receptor Antagonist
  • Antihypertensive Agents
• Drug: GROUP C: Chlorthalidone
  GROUP C: Treatment monotherapy: Chlorthalidone 12,5 mg once daily during 12 weeks. If the goals of blood pressure are uncontrolled at week 6, the dose will be increase to Chlorthalidone 25 mg once daily.
  Other Names:

  • Sodium Chloride Symporter Inhibitors
  • Antihypertensive Agents
  • Diuretics

Study Arms

• Experimental: GROUP A: Valsartan plus Chlorthalidone
  GROUP A: Combination therapy of Valsartan plus Chlorthalidone. Valsartan 80 mg/Chlorthalidone 12,5 mg. Once daily during 12 weeks.
  Intervention: Drug: GROUP A: Valsartan plus Chlorthalidone
• Experimental: GROUP B: Valsartan
  GROUP B: Treatment with Monotherapy. Valsartan 80 mg. Once daily during 12 weeks.
  Intervention: Drug: GROUP B: Valsartan
• Experimental: GROUP C: Chlorthalidone
  GROUP C: Treatment with Monotherapy. Chlorthalidone 12,5 mg. Once daily during 12 weeks.
  Intervention: Drug: GROUP C: Chlorthalidone

• Publications *: Manzur F, Rico A, Romero JD, Rodriguez-Martinez CE. Efficacy and Safety of Valsartan or Chlorthalidone vs. Combined Valsartan and Chlorthalidone in Patients With Mild to Moderate Hypertension: The VACLOR Study. Clin Med Insights Cardiol. 2018 Sep 3;12:1179546818796482. doi: 10.1177/1179546818796482. eCollection 2018.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 7, 2013): 124
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patient with diagnosis of arterial hypertension defined as:
• Systolic blood pressure greater or equal to 140 and lower than 180 mmHg
• Diastolic blood pressure greater or equal to 90 and lower than 110 mmHg
• Non controlled patients with antihypertensive treatment (blood pressure values: Systolic blood pressure > 140 mmHg and/or Diastolic blood pressure > 90 mmHg) or patients antihypertensive treatment-naïve.
• Likelihood of attending consultations according to the trial chronogram.
• Informed Consent Signature.

Exclusion Criteria:

• Diagnosis of severe or malignant arterial hypertension defined as:
• Systolic blood pressure greater or equal to 180 mmHg
• Diastolic blood pressure greater or equal to 110 mmHg
• Patients with secondary arterial hypertension of any etiology.
• Pregnant women or women with childbearing potential who are not using appropriate contraception methods; women planning to become pregnant during the trial.
• Patients with history of Acute Myocardial Infarction o Angina Pectoris within the 6 months prior to the trial initiation.
• Diagnosis of Cerebrovascular Disease (CVD) o Transient Ischemic Attack (TIA) within the 6 previous months.
• Patients with Severe Renal Disease defined by serum Creatinine levels higher than 1.5 mg/dl.
• Diagnosed or suspected unilateral or bilateral renal artery stenosis.
• History of non remitting cancer within the 5 years prior to the trial initiation.
• Patients with Hypokalemia or Hyperkalemia.
• Patients receiving Valsartan or Chlortalidone during the 14 previous days.
• Patients with known hypersensitivity to Valsartan or Chlorthalidone.
• Unstable patients with antecedent of hospitalization within the 4 days prior to their enrollment in the trial.
• Patients with history of drugs and alcohol abuse within the last year.
• Patients who have taken part in other clinical trial within the 4 weeks prior to the initiation of this research.
• Patients with any other clinical condition that the investigator deems may affect the patient follow-up.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Colombia, Ecuador

Administrative Information

• NCT Number: NCT01850160
• Other Study ID Numbers: 005-12 HTA
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Farma de Colombia SA
• Original Responsible Party: Same as current
• Current Study Sponsor: Farma de Colombia SA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Juan D Romero, MD; Farma de Colombia SA

• PRS Account: Farma de Colombia SA
• Verification Date: March 2015