Efficacy and Safety of Telmisartan in Hypertensive Patients With Mild/Moderate or Severe Renal Impairment or Requiring Hemodialysis

Study Overview
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Brief Summary
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To evaluate the safety and efficacy, in particular with regard to renal function of telmisartan at the doses of 40 mg and 80 mg in hypertensive patients with moderate to endstage renal impairment after 12 weeks of treatment

Official Title
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An Open-labeled, Placebo run-in, Multicentre Study to Investigate the Efficacy and Safety of Telmisartan (40 and 80 mg QD p.o.) in 3 Strata of Mild to Moderate Hypertensive Patients (Sitting Diastolic Blood Pressure ≥ 90 mmHg and ≤ 109 mmHg From Office Cuff Measurement) With Mild/Moderate or Severe Renal Impairment or Requiring Maintenance Hemodialysis. (ESPRIT Study = Efficacy and Safety in Patients With Renal Impairment Treated With Telmisartan)

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Telmisartan low dose
* Drug: Telmisartan high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mild to moderate hypertension, sitting diastolic BP ≥ 90 mmHg and BP ≤ 109 mmHg at visit 2 No increase of serum creatinine over 30% within 6 months before the trial Stable renal insufficiency with a serum creatinine between 200 and 600 µmol/l or maintenance of hemodialysis Stable proteinuria of at least 500 mg/24h No change in hemodialysis regimen within the last two months prior to visit 1 18 years of age or more Ability to provide written informed consent in accordance with good clinical practice and local registration Able to stop current antihypertensive therapy (ACE-Inhibitors or angiotensin II receptor subtype 1- Blocker) without risk to the patient Exclusion Criteria: Pre-menopausal women (last menstruation ≤ 1 year prior to start of run-in-phase) who: are not surgically sterile; and/or are nursing are of child-bearing potential and are NOT practicing acceptable means of birth control, do NOT plan to continue using this method throughout the study and do NOT agree to submit to periodic pregnancy testing during participation in studies of ≥ 3-months duration. Acceptable methods of birth control include oral, implantable or injectable contraceptives Known or suspected renovascular hypertension Mean sitting SBP ≥ 180 mmHg or mean sitting DBP ≥110 mmHg during any visit of the placebo run-in phase Hepatic dysfunction as defined by the following laboratory parameters: serum glutamate pyruvate transaminase (ALT) or serum glutamate oxaloacetate transaminase (AST) > than 2 times the upper limit of normal range Bilateral renal artery stenosis; renal artery stenosis in a solitary kidney, patients postrenal transplant or with only one kidney Clinically relevant hypo- or hyperkalaemia Uncorrected volume depletion Uncorrected sodium depletion Primary aldosteronism Hereditary fructose intolerance Biliary obstructive disorders Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II antagonists History of drug or alcohol abuse within 6 months Chronic administration of any medications known to affect blood pressure, except medication allowed by the protocol (ß-blocker, alpha-blocker, calcium antagonists, clonidine, minoxidil, and diuretics) Any investigational therapy within one month of signing the informed consent form Known hypersensitivity to any component of the formulation Has no contra-indication to a placebo run-in period (e.g. unstable angina within the past 3 months, stroke within the past 6 months or myocardial infarction or cardiac surgery within the past 3 months) Any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of telmisartan Compliance < 70% during run-in period (defined by pill count) History of heart failure, malignancy, or any disorders requiring immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan<br> | Drug: Telmisartan low dose<br> <br> Drug: Telmisartan high dose<br>* patients switch to high dose if mean SBP >= 85 mmHg after 4 weeks of treatment<br>Drug: Placebo<br>* Run-in phase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in seated diastolic blood pressure (DBP) at trough |  | 12 weeks after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in seated systolic blood pressure (SBP) at trough |  | 12 weeks after start of treatment | 
| Frequency of response categories of blood pressure | Categories: BP normal DBP control DBP response SBP response BP high normal | After 12 weeks of treatment | 
| Changes from baseline in proteinuria |  | 12 weeks after start of treatment | 
| Change in electrolyte excretion |  | 12 weeks after start of treatment | 
| Area under the telmisartan plasma concentration-time curve |  | Day 7 and 12 weeks after start of treatment | 
| Maximum plasma concentration (Cmax) of telmisartan |  | Day 7 and 12 weeks after start of treatment | 
| Time to peak (Tmax) plasma concentrations of telmisartan |  | Day 7 and 12 weeks after start of treatment | 
| Extent of protein binding of telmisartan | equilibrium dialysis with subsequent determination of protein-bound telmisartan fraction | Day 7 and 12 weeks after start of treatment |