Ignite Creation Date:
2024-05-06 @ 12:21 PM
Last Modification Date:
2024-10-26 @ 12:57 PM
Study NCT ID:
NCT03738761
Status:
COMPLETED
Last Update Posted:
2020-09-02
First Post:
2018-10-30
Brief Title:
Management of Newly Diagnosed and Uncontrolled Hypertension With Fixed-Dose Combination of PerindoprilAmlodipine and PerindoprilIndapamideAmlodipine
Sponsor:
KRKA
Organization:
KRKA
Study Overview
Official Title:
Fixed-Dose Combination of PerindoprilAmlodipine Amlessa and Fixed-Dose Combination of PerindoprilIndapamide Amlodipine Co-Amlessa - Contribution to Management in Newly Diagnosed and Uncontrolled Hypertensive Patients
Status:
COMPLETED
Status Verified Date:
2019-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRECIOUS
Brief Summary:
PRECIOUS Study aims to evaluate the efficacy and safety of therapy with fixed-dose combination FDC of perindoprilamlodipine Amlessa and FDC of perindoprilindapamideamlodipine Co-Amlessa on blood pressure reduction in both previously untreated patients and patients with previous antihypertensive therapy
Adult patients with AH who are treatment-naïve with systolic blood pressure SBP from 150 mmHg or higher ANDOR diastolic blood pressure DBP from 95 mmHg or higher SBP 150 mm ANDOR DBP 90 mmHg for patients with type 2 diabetes mellitus and uncontrolled patients on mono dual or triple antihypertensive therapy with systolic blood pressure SBP from 140 mmHg or higher ANDOR diastolic blood pressure DBP from 90 mmHg or higher SBP 140 ANDOR DBP 85 mmHg for patients with type 2 diabetes mellitus will be invited to participate in this study
During 16-week trial seven study visits are planned At first study visit physical examination medical history BP measurement electrocardiogram ECG laboratory analysis and of Ambulatory Blood Pressure Measurement ABPM will be performed Based on their previous antihypertensive therapy patients will receive to treatment with either Amlessa or Co-Amlessa for the duration of 16 weeks and blood pressure measurements laboratory investigations and patient interviews will be performed at study follow-up visits to assess the treatment efficacy proportion of patients reaching normal office blood pressure after 16 weeks of treatment and safety
Adult patients with AH who are treatment-naïve with systolic blood pressure SBP from 150 mmHg or higher ANDOR diastolic blood pressure DBP from 95 mmHg or higher SBP 150 mm ANDOR DBP 90 mmHg for patients with type 2 diabetes mellitus and uncontrolled patients on mono dual or triple antihypertensive therapy with systolic blood pressure SBP from 140 mmHg or higher ANDOR diastolic blood pressure DBP from 90 mmHg or higher SBP 140 ANDOR DBP 85 mmHg for patients with type 2 diabetes mellitus will be invited to participate in this study
During 16-week trial seven study visits are planned At first study visit physical examination medical history BP measurement electrocardiogram ECG laboratory analysis and of Ambulatory Blood Pressure Measurement ABPM will be performed Based on their previous antihypertensive therapy patients will receive to treatment with either Amlessa or Co-Amlessa for the duration of 16 weeks and blood pressure measurements laboratory investigations and patient interviews will be performed at study follow-up visits to assess the treatment efficacy proportion of patients reaching normal office blood pressure after 16 weeks of treatment and safety
Detailed Description:
PRECIOUS study is an interventional open-label prospective international multi-centre Phase IV clinical trial Phase III for countries without marketing authorisation for Co-Amlessa
The purpose of the study is to establish the efficacy and safety of fixed-dose combination FDC of perindoprilamlodipine Amlessa and FDC of perindoprilindapamideamlodipine Co-Amlessa in wide populations of newly diagnosed and uncontrolled patients with arterial hypertension AH with special focus on effective continuous 24-hour blood pressure BP control The purpose is also to establish the correlation between 24-hour central and peripheral BP
Perindopril indapamide and amlodipine are well known and extensively studied antihypertensive monotherapies Clinical data and safety analyses provided are substantial body of evidence that perindopril indapamide and amlodipine which have been used for more than 15 years are safe and well tolerated drugs Perindopril indapamide and amlodipine have complementary actions in reducing BP Combining perindopril and amlodipine or perindopril indapamide and amlodipine could improve adherence in uncontrolled hypertensive patients Namely the combinations would reduce the number of tablets to be taken by patient and thus simplify the treatment regimen and are therefore expected to facilitate long-term adherence to antihypertensive therapy which justifies their use Both combinations could also improve safety profile which would be beneficial from the tolerability point of view Namely when calcium channel blockers CCB and angiotensin converting enzyme inhibitors ACEI are used in combination there is a potential for lower incidence of peripheral oedema caused by CCB Similarly the incidence of ACEI-associated cough is attenuated by CCBs including amlodipine
This study aims evaluate the effect of therapy with Amlessa and Co-Amlessa on the blood pressure reduction in patients with essential arterial hypertension AH who are naïve with systolic blood pressure SBP from 150 mmHg or higher ANDOR diastolic blood pressure DBP from 95 mmHg or higher SBP 150 ANDOR DBP 90 mmHg for patients with type 2 diabetes mellitus and in uncontrolled patients on mono dual or triple antihypertensive with SBP from 140 mmHg or higher ANDOR DBP from 90 mmHg or higher SBP 140 ANDOR DBP 85 mmHg for patients with type 2 diabetes mellitus An objective of this trial is also to evaluate the safety of therapy with Amlessa and Co-Amlessa according to the frequency and severity of AR in patients with essential AH Overall 510 patients are planned to conclude the assessment and to be analysed In per-protocol analysis 450 patients are expected In order to allow for the estimated drop-out rate up to 570 patients are expected to be screened
All patients start with an initial screening which is performed one day before visit 1 to verify eligibility After inform consent signature and before therapy is allocated complete medical history physical examination with measurements of heart rate HR body weight and height lipid measurements and laboratory analysis including pregnancy test BP ambulatory blood pressure measurement ABPM and electrocardiogram ECG are performed Patients take the last doses of previous AH therapy on the day of the screening visit At Visit 1 day 0 the data from ABPM device is collected average BP central BP HR pulse wave velocity PWV and Aortic augmentation index BP and HR measurements are repeated Based on data gathered from all previous examinations on visit -1 and visit 1 investigator verifies patients eligibility Patients will not be randomized to treatment All eligible patients are assigned to start receiving any of the two study medication Amlessa and Co-Amlessa according to their previous antihypertensive therapy and as described in the protocol inclusion criteria Patients on previous perindopril and amlodipine therapy will be automatically assigned to Co-Amlessa group Patient starts taking the study medication on day of the visit 1 day 0
The total active treatment duration is 16 weeks with maximal allowed prolongation of 3 additional days per each of the four treatment periods due to possible unpredicted causes for delay in the follow-up visits The whole trial treatment schedule was determined on the basis of published pharmacological data for all active substances in study medications During the active treatment period each patient orally consumes one unit of assigned study medication once daily at about the same time each day 3 hours preferably in the morning and before a meal
At visit 2 on day 28 of the treatment period BP HR measurements safety assessing laboratory investigations serum creatinine serum potassium ALT AST GammaGT are repeated Patients compliance is assessed and safety assessment is carried out by the interview After the control of patient status the decision is made to maintain the treatment if sufficient normal office BP was reached or to change the treatment in accordance with protocol treatment model Normal office BP is defined as SBP 140 mmHg and DBP 90 mmHg patients with type 2 diabetes mellitus SBP 140 mmHg and DBP 85 mmHg
At Visit 3 on day 56 of the active treatment period BP HR measurements measurements lipid measurements and safety assessing laboratory investigations serum creatinine serum potassium ALT AST GammaGT are repeated Patients compliance is assessed and safety assessment is carried out by the interview After the control of patient status the decision is made to maintain the treatment if sufficient normal office BP was reached or to change the treatment in accordance with protocol treatment model Normal office BP is defined as SBP 140 mmHg and DBP 90 mmHg patients with type 2 diabetes mellitus SBP 140 mmHg and DBP 85 mmHg
At Visit 4 on day 84 of the active treatment period BP HR measurements measurements are repeated Patients compliance is assessed and safety assessment is carried out by the interview After the control of patient status the decision is made to maintain the treatment if sufficient normal office BP was reached or to change the treatment in accordance with protocol treatment model Normal office BP is defined as SBP 140 mmHg and DBP 90 mmHg patients with type 2 diabetes mellitus SBP 140 mmHg and DBP 85 mmHg
At Visit -5 on day 111 ABPM device is installed Blood samples are taken to provide the results of laboratory analysis the next day on visit 5 final visit At Visit 5 on day 112 the final efficacy and safety evaluation are carried out including patients adherence Physical examination with BP PWV and HR measurements lipid measurements laboratory analysis and ABPM are performed ABPM device is removed on the same day and the data from device is collected average BP central BP HR PWV and Aortic augmentation index Completion of all the procedures at Visit 5 determines the end of the patients involvement in this clinical trial After this patients further antihypertensive regimen is left to the discretion of the investigator
Once enrolled patients can be excluded before the protocol defined end of therapy due to patients decision or loss-to-follow-up patient non-compliance or safety issues as defined in the study protocol Concomitant therapy with other drugs is avoided in this study if possible
The primary efficacy endpoint is the responder rate at final visit Precisely this is defined to be the proportion of patients reaching normal blood pressure at Visit 5 after 16 weeks Normal office BP is defined as SBP 140 mmHg and DBP 90 mmHg patients with type 2 diabetes mellitus SBP 140 mmHg and DBP 85 mmHg It will be assessed with the two-sided equal-tails Clopper-Pearson exact 95-confidence interval for a population proportion
This trial is going to be conducted in compliance with the approved protocol and in accordance with the principles of Good Clinical Practice GCP with its corresponding Directives and Declaration of Helsinki Data management is carried out by the sponsor according to the data management plan sponsors standard operating procedures SOPs and GCP Data to be collected according to the study protocol and amendments if any will be recorded in electronic case report forms eCRF
The purpose of the study is to establish the efficacy and safety of fixed-dose combination FDC of perindoprilamlodipine Amlessa and FDC of perindoprilindapamideamlodipine Co-Amlessa in wide populations of newly diagnosed and uncontrolled patients with arterial hypertension AH with special focus on effective continuous 24-hour blood pressure BP control The purpose is also to establish the correlation between 24-hour central and peripheral BP
Perindopril indapamide and amlodipine are well known and extensively studied antihypertensive monotherapies Clinical data and safety analyses provided are substantial body of evidence that perindopril indapamide and amlodipine which have been used for more than 15 years are safe and well tolerated drugs Perindopril indapamide and amlodipine have complementary actions in reducing BP Combining perindopril and amlodipine or perindopril indapamide and amlodipine could improve adherence in uncontrolled hypertensive patients Namely the combinations would reduce the number of tablets to be taken by patient and thus simplify the treatment regimen and are therefore expected to facilitate long-term adherence to antihypertensive therapy which justifies their use Both combinations could also improve safety profile which would be beneficial from the tolerability point of view Namely when calcium channel blockers CCB and angiotensin converting enzyme inhibitors ACEI are used in combination there is a potential for lower incidence of peripheral oedema caused by CCB Similarly the incidence of ACEI-associated cough is attenuated by CCBs including amlodipine
This study aims evaluate the effect of therapy with Amlessa and Co-Amlessa on the blood pressure reduction in patients with essential arterial hypertension AH who are naïve with systolic blood pressure SBP from 150 mmHg or higher ANDOR diastolic blood pressure DBP from 95 mmHg or higher SBP 150 ANDOR DBP 90 mmHg for patients with type 2 diabetes mellitus and in uncontrolled patients on mono dual or triple antihypertensive with SBP from 140 mmHg or higher ANDOR DBP from 90 mmHg or higher SBP 140 ANDOR DBP 85 mmHg for patients with type 2 diabetes mellitus An objective of this trial is also to evaluate the safety of therapy with Amlessa and Co-Amlessa according to the frequency and severity of AR in patients with essential AH Overall 510 patients are planned to conclude the assessment and to be analysed In per-protocol analysis 450 patients are expected In order to allow for the estimated drop-out rate up to 570 patients are expected to be screened
All patients start with an initial screening which is performed one day before visit 1 to verify eligibility After inform consent signature and before therapy is allocated complete medical history physical examination with measurements of heart rate HR body weight and height lipid measurements and laboratory analysis including pregnancy test BP ambulatory blood pressure measurement ABPM and electrocardiogram ECG are performed Patients take the last doses of previous AH therapy on the day of the screening visit At Visit 1 day 0 the data from ABPM device is collected average BP central BP HR pulse wave velocity PWV and Aortic augmentation index BP and HR measurements are repeated Based on data gathered from all previous examinations on visit -1 and visit 1 investigator verifies patients eligibility Patients will not be randomized to treatment All eligible patients are assigned to start receiving any of the two study medication Amlessa and Co-Amlessa according to their previous antihypertensive therapy and as described in the protocol inclusion criteria Patients on previous perindopril and amlodipine therapy will be automatically assigned to Co-Amlessa group Patient starts taking the study medication on day of the visit 1 day 0
The total active treatment duration is 16 weeks with maximal allowed prolongation of 3 additional days per each of the four treatment periods due to possible unpredicted causes for delay in the follow-up visits The whole trial treatment schedule was determined on the basis of published pharmacological data for all active substances in study medications During the active treatment period each patient orally consumes one unit of assigned study medication once daily at about the same time each day 3 hours preferably in the morning and before a meal
At visit 2 on day 28 of the treatment period BP HR measurements safety assessing laboratory investigations serum creatinine serum potassium ALT AST GammaGT are repeated Patients compliance is assessed and safety assessment is carried out by the interview After the control of patient status the decision is made to maintain the treatment if sufficient normal office BP was reached or to change the treatment in accordance with protocol treatment model Normal office BP is defined as SBP 140 mmHg and DBP 90 mmHg patients with type 2 diabetes mellitus SBP 140 mmHg and DBP 85 mmHg
At Visit 3 on day 56 of the active treatment period BP HR measurements measurements lipid measurements and safety assessing laboratory investigations serum creatinine serum potassium ALT AST GammaGT are repeated Patients compliance is assessed and safety assessment is carried out by the interview After the control of patient status the decision is made to maintain the treatment if sufficient normal office BP was reached or to change the treatment in accordance with protocol treatment model Normal office BP is defined as SBP 140 mmHg and DBP 90 mmHg patients with type 2 diabetes mellitus SBP 140 mmHg and DBP 85 mmHg
At Visit 4 on day 84 of the active treatment period BP HR measurements measurements are repeated Patients compliance is assessed and safety assessment is carried out by the interview After the control of patient status the decision is made to maintain the treatment if sufficient normal office BP was reached or to change the treatment in accordance with protocol treatment model Normal office BP is defined as SBP 140 mmHg and DBP 90 mmHg patients with type 2 diabetes mellitus SBP 140 mmHg and DBP 85 mmHg
At Visit -5 on day 111 ABPM device is installed Blood samples are taken to provide the results of laboratory analysis the next day on visit 5 final visit At Visit 5 on day 112 the final efficacy and safety evaluation are carried out including patients adherence Physical examination with BP PWV and HR measurements lipid measurements laboratory analysis and ABPM are performed ABPM device is removed on the same day and the data from device is collected average BP central BP HR PWV and Aortic augmentation index Completion of all the procedures at Visit 5 determines the end of the patients involvement in this clinical trial After this patients further antihypertensive regimen is left to the discretion of the investigator
Once enrolled patients can be excluded before the protocol defined end of therapy due to patients decision or loss-to-follow-up patient non-compliance or safety issues as defined in the study protocol Concomitant therapy with other drugs is avoided in this study if possible
The primary efficacy endpoint is the responder rate at final visit Precisely this is defined to be the proportion of patients reaching normal blood pressure at Visit 5 after 16 weeks Normal office BP is defined as SBP 140 mmHg and DBP 90 mmHg patients with type 2 diabetes mellitus SBP 140 mmHg and DBP 85 mmHg It will be assessed with the two-sided equal-tails Clopper-Pearson exact 95-confidence interval for a population proportion
This trial is going to be conducted in compliance with the approved protocol and in accordance with the principles of Good Clinical Practice GCP with its corresponding Directives and Declaration of Helsinki Data management is carried out by the sponsor according to the data management plan sponsors standard operating procedures SOPs and GCP Data to be collected according to the study protocol and amendments if any will be recorded in electronic case report forms eCRF
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2017-001596-23 | EUDRACT_NUMBER | None | None |