Adult patient with mild to moderate essential hypertension and microalbuminuria. MedDRA version: M15 Level: LLT Classification code 10020772
Conditions
Interventions
Product Name: Diovan 80 mg kapszula
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Valsartan
Current Sponsor code: VAL489
Concentration unit: mg milligram(s)
Concentration type: equal
Concent
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female subjects, age between 18-75 years inclusive. • Patients with mild to moderate hypertension with a MSDBP >= 85 and = 20 mg/l) at Visit 1 (day -21). • Written informed consent to participate in the study prior to any study procedures. • Confirmation of MAU determined in the first morning urine samples performed at Visit 2 (day -14) and Visit 3 (day -7). MAU is defined for male patients as UACR >= 2.5 mg/mmol and = 3.5 mg/mmol and = 85 mm Hg and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any kind of kidney disease, which is not primarily caused by diabetes or hypertension. 2. Any clinically relevant abnormality in kidney ultrasound, in the urine sediment or urine analysis with dipstick at Visit 1 (decision for exclusion due to clinically relevant abnormalities for protein, glucose and pH measured via dipstick is at discretion of the investigator). 3. Evidence of renal impairment as determined by any one of the following: Serum creatinine clearance 1.25 x ULN at Visit 1, a history of dialysis, or a history of nephrotic syndrome. 4. Serum potassium values 5.5 mmol/l at Visit 1 5. Any medical condition which might significantly alter the urinary excretion of albumin 6. Fluid depletion; the patient is to be instructed to drink at least 2 l/day, especially during the last day prior Visit 1-4, 9 and 12. 7. Unwillingness or inability to avoid extensive exercise (any sport activity lasting longer than 30 minutes) during the last day prior Visit 1-4, 9 and 12. 8. Active urinary infection 9. Vaginal discharge/fluor and/or vaginal infection 10. Active systemic infection and/or fever 11. Current obstruction of the urinary tract or difficulty in voiding due to mechanical as well as inflammatory conditions which is likely to require intervention during the course of the study or is regarded as clinically meaningful by the investigator 12. Severe hypertension defined as grade 3 of WHO classification; mean sitting diastolic blood pressure MSDBP >=110 mm Hg and/or mean sitting systolic blood pressure (MSSBP) >=180 mm Hg 13. Known history of hypotensive symptoms or orthostatic hypotension 14. Type 1 Diabetes mellitus 15. Uncontrolled treated Type 2 Diabetes mellitus with poor glucose control defined as HbA1c > 8.0 % at Visit 1 16. Inability to discontinue all prior anti-hypertensive medications safely for a period of 3 weeks, as required by the protocol 17. Administration of any agent indicated for the treatment of hypertension after the visit 1, permitted exception of those anti-hypertensive medications requiring tapering down commencing at Visit 1 18. Mandatory indication for any concomitant medication for coronary artery disease or any other disease that is not allowed during this study 19. Known or suspected contraindications as listed in the basic prescribing information, including history of allergy to ARBs and ACEIs, incl. consideration on contraindications of free add-on medication amlodipine and HCTZ 20. History of hypertensive encephalopathy, coronary artery bypass surgery, percutaneous transluminal angioplasty, transient ischemic cerebral attack, stroke or myocardial infarction during the last 12 months prior to Visit 1 21. Known Keith-Wagener grade III or IV hypertensive retinopathy 22. Evidence of a secondary form of hypertension, to include coarctation of the aorta, hyperaldosteronism, renal artery stenosis, or pheochromocytoma 23. History of heart failure 24. Second or third degree heart block without a pacemaker 25. Concomitant unstable angina pectoris 26. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia 27. Clinically significant valvular heart disease 28. Evidence of hepatic disease or cholestasis as determined by any one of the following: ALT or AST values 2 x ULN at visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt 29. S
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the difference in microalbuminuria (MAU) in form of urinary albumin excretion measured as urinary albumin/creatinine ratio (UACR) in the first morning urine after treatment with valsartan 320 mg/lisinopril 20 mg combination compared to lisinopril 40 mg monotherapy and to valsartan 320 mg monotherapy from baseline to Week 30 in hypertensive subjects with previously diagnosed MAU (baseline).;Secondary Objective: 1. To compare the effects of valsartan /lisinopril combination vs. monotherapy of each study drug on proportion of patients who return to normalization of urinary albumin excretion (week 30). 2. To evaluate the proportion of patients who proceed to macroalbuminuria at Week 30 3. To evaluate effects of valsartan, lisinopril and their combination on the reduction of MAU in patients who achieve the target blood pressure. 4. To compare the effects of valsartan, lisinopril and their combination on the proportion of patients, who achieve the target blood pressure and who return at Week 30 to normalization of UA excretion. 5. To compare the effects of valsartan, lisinopril and their combination on the change of creatinine clearance. 6. To evaluate the effects of valsartan, lisinopril and their combination on markers of vascular inflammation e. g. Hs-CRP, TNFalpha IL-6. 7. To evaluate safety and tolerability of valsartan, lisinopril and their combination. ;Primary end point(s): The primary objective is to demonstrate the reduction in MAU in form of urinary albumin excretion measured as urinary albumin/creatinine ratio (UACR) in the first morning urine from baseline to Week 30 in hypertensive subjects with previously diagnosed MAU (baseline). The primary comparison is between the combination group of Valsartan 320 mg/Lisinopril 20 mg and the monogroups of Lisinopril 40 mg and Valsartan 320 mg. | — |
Countries
Hungary
Outcome results
None listed