A randomized, open-label, multicentric parallel group study to assess the impact of supportive measures on the drug adherence of patients with essential hypertension treated with Valsartan or Valsartan plus HCTZ for 34 weeks with or without respective measures - VALIDATE

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-003605-82-DE
• Date of registration: 05/10/2005
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: A randomized, open-label, multicentric parallel group study to assess the impact of supportive measures on the drug adherence of patients with essential hypertension treated with Valsartan or Valsartan plus HCTZ for 34 weeks with or without respective measures - VALIDATE
• Scientific title: A randomized, open-label, multicentric parallel group study to assess the impact of supportive measures on the drug adherence of patients with essential hypertension treated with Valsartan or Valsartan plus HCTZ for 34 weeks with or without respective measures - VALIDATE
• Date of first enrolment: 15/11/2005
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003605-82
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Supportive measures are blinded for centers not randomized to use of them If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Use / no use of supportive measures

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients >= 18 years
2. Patients with mild essential hypertension (MSDBP >= 90 mmHg and < 100 mmHg and/or MSSBP >= 140 mmHg and < 160 mmHg) at visits 1 and 2 not having been treated with antihypertensive drugs before or not having been treated with antihypertensive drugs for at least one year prior to visit 1
3. Written informed consent to participate in the study prior to any study procedures

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. MSSBP = 160 mmHg and/or MSDBP = 100 mmHg at any time between Visit 1 and 2
2. Patients currently requiring / likely to require any regular long-term drug treatment, i.e. for more than 28 days, (e.g., asthma, COPD, diabetes, rheumatoid arthritis, pain medication, depression, psychotropic drugs, inflammatory bowel disease, estrogen replacement therapy, thyroid hormones, hypercholersterolemia, oral contraception, oral anticoagulation).
3. History of hypersensitivity to valsartan or HCTZ, inactive ingredients of these study drugs or to drugs with similar chemical structures
4. A history of cardiovascular disease, including angina pectoris, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, transient ischemic attack, stroke, and peripheral artery disease
5. Known Keith-Wagener grade III or IV hypertensive retinopathy
6. Second or third degree heart block without a pacemaker, concurrent potentially life threatening arrhythmia or symptomatic arrhythmia, clinically significant valvular heart disease
7. Heart failure NYHA II -IV
8. Evidence of a secondary form of hypertension, to include coarctation of the aorta, hyperaldosteronism, Cushing’s disease, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease
9. Diabetes mellitus type I or diabetes mellitus type II requiring drug treatment
10. Evidence of hepatic disease as determined by AST (SGOT) or ALT (SGPT) values > 2 x ULN at Visit 1, severe liver failure, biliary cirrhosis, cholestasis
11. A history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt
12. Evidence of renal impairment as determined by one of the followings: serum creatinine > 1.5 x ULN at Visit 1, a history of dialysis, or a history of nephrotic syndrome. If creatinine is found to be between 1.5 and 2 x UNL, a retest can be performed prior to initiation of treatment
13. Therapy resistant hypokalaemia, hyponatraemia, hypercalcaemia, or symptomatic hyperuricaemia
14. Any severe, life-threatening disease within the past five years
15. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug.
16. Any surgical or medical condition which, at the discretion of the investigator, places the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of the study or completing the trial period
17. History of drug or alcohol abuse within the last 2 years
18. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lifes before enrollment, whichever is longer
19. History of noncompliance with medical regimens, or patients unwilling to comply with the study protocol
20. Persons directly involved in the execution of this protocol/study
21. Inability to communicate and comply with all study requirements
22. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
23. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml).
24. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of bec

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with essential hypertension
MedDRA version: M15 Level: LLT Classification code 10015488

Intervention(s)

Trade Name: Diovan 160 mg
Product Name: Diovan 160 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Valsartan
Current Sponsor code: VAL489
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-

Trade Name: CoDiovan 160 mg/12,5 mg
Product Name: CoDiovan 160 mg /12,5 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Valsartan
Current Sponsor code: VAL489
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 160-
INN or Proposed INN: Hydrochlorothiazide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Primary Outcome(s)

Main Objective: To demonstrate that supportive measures improve drug adherence in patients with mild essential hypertension treated with valsartan 160 mg or valsartan 160 mg plus HCTZ 12.5 mg for 34 weeks. To assess adherence, data on compliance and persistence will be collected.
For primary efficacy the daily proportion of patients taking one tablet of the prescribed hypertensive therapy between 07:00 and 11:00AM will be assessed using an electronic monitor (MEMS) and will be compared between randomized groups over the course of the study.

Primary end point(s): Detailed analysis of patient adherence is the focus of the primary analysis. Any concomitant therapies reported during the trials will be listed in a table format.
For each patient, the relative time is defined as the time (in days) since date of study entry. For each patient, a longitudinal binary outcome variable Zit will be defined as follows
Zit = 1 if patient i has opened the MEMS monitor exactly once between 07:00 and 11:00 AM on day t.
Zit = 0 otherwise
Comparison of binary time series are realized using logistic regression where dependence among observations from a given patient over time is taken into account through a generalized estimating equation (GEE) approach with a first order autoregressive covariance structure and accounting for the effect of clustering. The effect of intervention will be tested using the above describe model by testing if either the coefficient for GROUP or for the interaction between GROUP and TIME are significantly different from zero.

Secondary Objective: Adherence to the prescribed regimen defines the patient’s general tendency to follow medical advice. It is therefore useful to define two substituent terms: (a) compliance, and (b) persistence. The former is defined as ‘the degree of correspondence between the patient’s actual dosing history and the prescribed dosing regimens. The latter is defined as ‘the time elapsed between the first dose taken and time of treatment discontinuation’. Both components will be compared between randomized groups over time.
To assess discrepancies between pill counts, Morisky questionnaire and electronic monitoring to estimate patient adherence to prescribed therapy
To assess the relation between drug exposure and BP reduction.
To assess the relation between drug exposure and the likelihood to switch to valsartan 160 mg plus HCTZ 12.5 mg
To assess the safety and tolerability of valsartan 160 mg and valsartan 160 mg plus HCTZ 12.5 mg.

Secondary ID(s)

CVAL489ADE24