hypertension
Conditions
Interventions
Trade Name: Tritace 2,5 mg tabletta
Pharmaceutical Form: Tablet
INN or Proposed INN: ramipril
CAS Number: 87333-19-5
Other descriptive name: RAMIPRIL
Concentration unit: mg milligram(s)
Concentration
Sponsors
Egis Pharmaceuticals PLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Mild and moderate (Grade 1 and 2) essential hypertension not controlled at ramipril or indapamide SR monotherapy administered at least 4 weeks. Definition of not controlled mild and moderate hypertension: systolic blood pressure [SBP] = 140 mmHg with or without diastolic blood pressure [DBP] = 90 mmHg, but SBP = 179 mmHg and DBP = 109 mmHg. 2. Male and female patients = 18 years, but =65 years) yes F.1.3.1 Number of subjects for this age range 23
Exclusion criteria
Exclusion criteria: 1. General contraindications of thiazide diuretics and/or ACE inhibitors a) Known hypersensitivity to indapamide or other sulphonamides, ramipril or any other ACE inhibitor or to any of the excipients b) History of angioedema (hereditary, idiopathic or due to previous angioedema with ACE inhibitors or AIIRAs) c) Secondary hypertension d) Extracorporeal treatments leading to contact of blood with negatively charged surfaces e) Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney f) Renal impairment defined as eGFR ULN j) Hyponatraemia i.e. se Sodium ULN l) Hyperuricemia i.e. se uric acid > ULN and judged clinically significant m) Congestive heart failure (NYHA III-IV.) n) Type 1 or uncontrolled Type 2 diabetes mellitus, i.e. HbA1C >8%, or patients on SGLT2 inhibitor treatment. o) Treatment with ARB, aliskiren or lithium p) Patients with hypotensive or haemodynamically unstable states q) Patients having a history of myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident (stroke), acute heart failure or transient ischaemic attack within the last six months 2. Any other anti-hypertensive drugs (other than ramipril and indapamide SR) used within 4 weeks prior to the screening visit. 3. Use of any enzyme-modifying drugs acting on cytochrome P450 (CYP) 3A4 enzymes via inhibition or induction within 28 days before day 1 of this trial. 4. Elderly patients < 80 years of age, but not in good physical and mental condition, who in the opinion of the Investigator will not tolerate reduction of BP until target of 140/80 mmHg (“fragile” elderly patients) 5. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, lactose intolerance or glucose-galactose malabsorption 6. History of drug or alcohol dependency or abuse within the last 2 years 7. Concurrent alcohol and/or drug abuse. 8. Any other condition, disease or therapy which in the Investigator’s opinion would pose a risk to the subject or interfere with the trial objectives. 9. Pregnancy and lactation period. All female patients with reproductive potential must have a negative pregnancy serum test at the time of the Screening visit and have to use adequate contraception during the study. 10. Known lack of subject compliance. 11. Participation in another clinical trial within the previous 30 days. 12. Persons directly involved in the execution of this protocol and their relatives. Females of childbearing potential must have negative serum pregnancy test at screening. (All females will be considered to be of childbearing potential unless they are postmenopausal i.e. amenorrhoeic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause or have been sterilized surgically i.e. bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the efficacy of co-administration of ramipril and indapamide SR in reduction of blood pressure in hypertensive patients whose blood pressure (BP) is not controlled by ramipril 5 mg, 10 mg or indapamide SR 1.5 mg alone.;Secondary Objective: To investigate the percentage of patients whose BP is either became controlled or met the criterion of response to therapy in different treatment groups and in pools at different dosages of ramipril administered concomitantly with indapamide SR. Response to therapy is defined as the reduction in SBP/DBP at Visit 7 reaches 20/10 mmHg comparing to the baseline values. To investigate the safety of co-administration of ramipril and indapamide SR in hypertensive patients. ;Primary end point(s): The primary endpoint is defined as a mean reduction of systolic blood pressure (SBP) after 10 weeks of treatment (measured on the last study visit before the medication is taken) compared to the baseline value (measured before the start of concomitant administration of ramipril and indapamide SR) in the treatment group the patient enrolled and irrespectively from the final therapy at the last visit.;Timepoint(s) of evaluation of this end point: 10 weeks of treatment(measured on the last study visit before the medication is taken) compared to the baseline value (measured before the start of concomitant administration of ramipril and indapamide SR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are defined as follows: 1. Mean reduction in diastolic blood pressure (DBP) after 10 weeks of treatment compared to the last DBP before the concomitant administration of ramipril and indapamide SR. 2. Mean reduction of SBP after 6 weeks of treatment compared to the last SBP before the concomitant administration of ramipril and indapamide SR. 3. Mean reduction of DBP after 6 weeks of treatment compared to the last DBP before the concomitant administration of ramipril and indapamide SR. 4. Percentage of patients whose BP is either controlled or responders (irrespectively of dose of ramipril) at Day 71 in the whole study population and in the treatment groups the patient enrolled. 5. Percentage of patients whose BP is either controlled or responders (irrespectively of dose of ramipril) at Day 99 in the whole study population and in the treatment groups the patient enrolled. 6. Percentage of patients whose BP is controlled or responders with administration of ramipril 5 mg/indapamide SR 1.5 mg and ramipril 10 mg/indapamide 1.5 mg, respectively at Day 99 in Group 1. 7. Percentage of patients whose BP is controlled with administration of ramipril 5 mg/indapamide 1.5 mg and ramipril 10 mg/indapamide 1.5 mg, respectively at Day 99 in Group 2. 8. Number of AEs reported as safety laboratory parameters out of normal range, which have clinical significance by judgement of the physician. 9. Number of Adverse events judged as related to the study treatment. Normalization of blood pressure means systolic blood pressure [SBP] < 140 mmHg with or without diastolic blood pressure [DBP] < 90 mmHg. However, based on the investigator’s decision, ramipril dose can be increased during the study in patients with SBP/DBP lower than 140/90 mmHg, but higher than recommended target blood pressure levels defined in the 2018 ESC/ESH Guidelines on the Management of Arterial Hypertension, who tolerate well the combination treatment. Respo | — |
Countries
Hungary
Contacts
Public ContactDept of Clin Pharm and Development
Egis Pharmaceuticals PLC
Outcome results
None listed