Study to Evaluate Efficacy of Micardis® (Telmisartan) and Valsartan in Patients With Mild-to-moderate Hypertension After Missing One Dose Using Ambulatory Blood Pressure Monitoring

Phase 4

Completed

• Conditions: Hypertension
• Interventions: Drug: Valsartan; Drug: Telmisartan; Drug: Placebo

• Registration Number: NCT02242318
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The primary aim of the trial is to compare telmisartan 80 mg to valsartan 160 mg in lowering diastolic blood pressure in patients who missed a dose of their medication, as measured by ABPM (change from baseline in mean DBP over 24 hours), and to compare telmisartan 80 mg to valsartan 160 mg in lowering DBP during the last six hours of the dosing interval at the end of a 6 to 8-week treatment period, as measured by ABPM (change from baseline)

Detailed Description

Not available

Study Timeline

• Study Start: 2001-09
• Primary Completion: 2002-09
• Status Verified: 2014-09
• Study First Submitted: 2014-09-16
• Study First Submitted QC: 2014-09-16
• Last Update Submitted: 2014-09-16
• Study First Posted: 2014-09-17
• Last Update Posted: 2014-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 440

Inclusion Criteria

1. Mild-to-moderate hypertension defined as a mean seated diastolic blood pressure of ≥ 95 mmHg and ≤ 109 mmHg, measured by manual cuff sphygmomanometer, at Visit 2
2. 24-hour mean DBP of ≥ 85 mmHg at Visit 3 as measured by ABPM
3. Age 18 years or older
4. Ability to stop any current antihypertensive therapy without risk to the patient (investigator's discretion)
5. Patient's written informed consent in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion Criteria

1. Pre-menopausal women (last menstruation ≤ 1 year prior to start of run-in period) who

   1. are not surgically sterile,
   2. are nursing,
   3. are of child-bearing potential and are NOT practising acceptable methods of birth control, or do NOT plan to continue practising an acceptable method throughout the study. Acceptable methods of birth control include oral, implantable or injectable contraceptives and Intra Uterine Devices (IUD)

2. Known or suspected secondary hypertension

3. Mean sitting SBP ≥180 mmHg or mean sitting DBP ≥110 mmHg during any visit of the placebo run-in period

4. Hepatic and/or renal dysfunction as defined by the following laboratory parameters:

   1. Serum Glutamate-Pyruvate-Transaminase (Alanine Aminotransferase) (SGPT (ALT)) or Serum Glutamate-Oxaloacetate-Transaminase (Aspartate Aminotransferase) (SGOT (AST)) > than 2 times the upper limit of normal range,
   2. Serum creatinine > 2.3 mg/dL (or > 203 μmol/l)

5. Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients postrenal transplant or with only one kidney

6. Clinically relevant sodium depletion, hypokalaemia or hyperkalaemia

7. Uncorrected volume depletion

8. Primary aldosteronism

9. Hereditary fructose intolerance

10. Biliary obstructive disorders

11. Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists

12. History of drug or alcohol dependency within six months prior to start of run-in period

13. Concomitant administration of any medications known to affect blood pressure, except medication allowed by the protocol

14. Any investigational therapy within one month of signing the informed consent form

15. Congestive heart failure (New York Heart Association (NYHA) functional class Congestive Heart Failure (CHF III-IV))

16. Unstable angina within the past three months prior to start of run-in period

17. Stroke within the past six months prior to start of run-in period

18. Myocardial infarction or cardiac surgery within the past three months prior to start of run-in period

19. Percutaneous Transluminal Coronary Angioplasty (PTCA) within the past three months prior to start of run-in period

20. Sustained ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the investigator

21. Hypertrophic obstructive cardiomyopathy, aortic stenosis, hemodynamically relevant stenosis of the aortic or mitral valve

22. Patients with insulin-dependent diabetes mellitus whose diabetes has not been stable and controlled for at least the past three months as defined by an HbA1C ≥ 10%

23. Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 Ante Meridiem (AM)

24. Known hypersensitivity to any component of the formulations

25. Any clinical condition which, in the opinion of the investigator would not allow safe completion of the protocol and safe administration of trial medication

26. Inability to comply with the protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Valsartan	Valsartan	low dose for two weeks, then up titration to high dose, once daily
Valsartan	Placebo	low dose for two weeks, then up titration to high dose, once daily
Placebo	Placebo	-
Telmisartan	Placebo	low dose for two weeks, then up titration to high dose, once daily
Telmisartan	Telmisartan	low dose for two weeks, then up titration to high dose, once daily

Primary Outcome Measures

Name	Time	Method
Change in 24 hour mean Diastolic blood pressure (DBP) after a missed dose	Baseline, Day 41, Day 55	measured by ambulatory blood pressure monitoring (ABPM)
Change in mean DBP during the last 6 hours of the 24 hour dosing interval	up to 8 weeks

Secondary Outcome Measures

Name	Time	Method
Change in 24-hour mean systolic blood pressure (SBP) after a missed dose	Baseline, Day 41, Day 55
Change in mean SBP during the last 6 hours of the 24-hour dosing interval	up to 8 weeks
Change in pulse pressure (PP)	up to 8 weeks
Change in 24-hour mean DBP after an active dose of study medication	up to 8 weeks
Change in 24-hour mean SBP after an active dose of study medication	up to 8 weeks
Change in mean seated trough SBP/DBP/PP in- clinic manual cuff sphygmomanometer after a missed dose	up to 8 weeks
Change in the mean seated trough SBP/DBP/PP in- clinic manual cuff sphygmomanometer after an active dose of study medication	up to 8 weeks
Responder rate measured by ABPM after a missed dose of study medication	Baseline, Day 41, Day 55	* ABPM DBP "control" (24-hour mean DBP \< 80 mmHg),; * ABPM DBP "response" (24-hour mean DBP \< 80 mmHg and/or reduction from baseline ≥ 10 mmHg),; * ABPM SBP "response" (24-hour mean SBP \< 130 mmHg and/or reduction from baseline ≥ 10 mmHg)
Responder rate measured by ABPM after an active dose of study medication	up to 8 weeks	* ABPM DBP "control" (24-hour mean DBP \< 80 mmHg),; * ABPM DBP "response" (24-hour mean DBP \< 80 mmHg and/or reduction from baseline ≥ 10 mmHg),; * ABPM SBP "response" (24-hour mean SBP \< 130 mmHg and/or reduction from baseline ≥ 10 mmHg)
Responder rate in- clinic manual trough cuff measurements after a missed dose of study medication	Baseline, Day 41, Day 55	* DBP "control" (DBP \< 90 mmHg),; * DBP "response" (DBP \< 90 mmHg and/or fall of ≥ 10 mmHg),; * SBP "response" (SBP \< 140 mmHg and/or fall of ≥ 10 mmHg),; * BP "normal" (SBP \< 130 mmHg and DBP \< 85 mmHg),; * BP "normal / high normal" (SBP \< 140 mmHg and DBP \< 90 mmHg).
Responder rate in- clinic manual trough cuff measurements after an active dose of study medication	up to 8 weeks	* DBP "control" (DBP \< 90 mmHg),; * DBP "response" (DBP \< 90 mmHg and/or fall of ≥ 10 mmHg),; * SBP "response" (SBP \< 140 mmHg and/or fall of ≥ 10 mmHg),; * BP "normal" (SBP \< 130 mmHg and DBP \< 85 mmHg),; * BP "normal / high normal" (SBP \< 140 mmHg and DBP \< 90 mmHg).
Number of patients with adverse events	up to 8 weeks
Change in 24-hour Pulse Pressure (PP) after a missed dose	Baseline, Day 41, Day 55