PROTOCOL OUTLINE TEMPLATE

HYPERTENSION / MEDICATION
AUTHORS: ANIS R., MALINA W., RUKIYE Ö. AND SARIA Z.
TITEL

 Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Study to Evaluate the Efficacy and
Safety of HSH-123 compared to placebo after 4 months Treatment in Patients with Essential Hypertension
RATIONALE

 Clinical problems:  Available interventions:  Incidence and prevalence:

 High blood pressure  Drug administration (e. g. ß-  Incidence of Hypertension:
 Heart failure Blocker, ACE-Hemmer…)  10-50% total Population

 Stroke  Life-style modification (sport,  Prevalence of Hypertension:

healthy food…)  44% women
 Angina pectoris
 51% men
 Heart attack
 With age the Hypertension
 Renal impairment increase
(Einschränkung der
Nierenfunktion)
 Circulation problems in the
legs (Durchblutungsstörung
der Beine)
OBJECTIVES

 Primary objective  Secondary objective

 To demonstrate the effect of HSH-123  Assess of safety and tolerability of HSH-
 Decrease blood pressure 123
 Decrease rate of cardiac deffects  A once daily schedule
DESIGN / PHASE

 Prospective-cohort Study
 Multi-Center
 Double-Blind
 Randomized
 Placebo-controlled
 Parallel group
 Phase II study
STUDY PLANNED DURATION

 Period of treatment  Period of treatment  Period of treatment duration

(4 months) (6 months) (4 months)
 First patient First  Last patient First  Last patient Last visit:
visit: 01.02.16 visit: 01.08.16 01.12.16
 First patient Last  First patient First  First patient First visit:
visit: 01.06.16 visit: 01.02.16 01.08.16
CENTER(S)/ COUNTRY(IES)

 26 centers in 3 countries
 Germany 14
 France 8
 India 4
PATIENTS / GROUP

 400 patients in 2 groups (age 52, 200 female and 200 male)
 Group 1 (randomized)
 Drug HSH-123 for 4 moths

 Group 2 (randomized)
 Placebo for 4 months
INCLUSION CRITERIA

 Informed concent from patient

 Level1 hypertension
 Systolic: 140 - 159 mmHg
 Diastolic: 90 - 99 mmHg
 Communicate and comply with all study requirements
 Compliance medication
EXCLUSION CRITERIA

 Severe Hypertension  History of

 History of  Angina pectoris
 Angioedema  Myocardial infarction
 drug-related  Coronary bypass surgery
 Pregnant / nursing women  Ischemic heart disease
 Diabetes mellitus  Surgical or percutaneous arterial
 Previous / current diagnosis of heart intervention of any kind
failure  Stroke
 Clinical significant valvular heart  Peripherale arterial disease
disease
CONCOMITANT MEDICATIONS

 Untreated or currently taking antihypertensive therapy e. g.:

 ACE-Hemmer
 Beta-Blockers
 Calcium Antagonists
STUDY PERIODS

 Definition and duration of study periode

 1 months screening
 4 months treatment
 1 months follow-up periods
 End-of-Study if there is serious adverse event, e. g.:
 Sickness
 Palpitation
 Dizziness
 Treatment duration
 4 months
 Study duration
 6 monhts
MEDICATION

 Investigational Drug
 HSH-123

 Comparative Drug
 Placebo
EFFICACY POINTS

 Primary endpoints
 Decrease blood pressure
 Safe patient with hypertension
 Angina pectoris
 Myocardial infarction
 Coronary bypass surgery
 Ischemic heart disease
 Surgical or percutaneous arterial intervention

 Secondary endpoints
 Safety and tolerability of drug HSH-123
TOLERABILITY / SAFETY ENDPOINTS

 All advers events

 Heart rate and blood pressure
QUALITY OF LIFE / PHARMACOECONOMIC ENDPOINTS

 Less stress
 Healthy mode of life
STUDY COMMITTEES

 EMA European Medicines Agancy

 IEC Independent Ethics Committee
 DSMB Data and Safety Monitoring Board
 IRB Institutional Review Board
VISIT AND ASSESSMENT SCHEDULE