Hypertension
Conditions
Keywords
Effectiveness and tolerability of Tarka, Hypertensive patients, Diabetes mellitus, Observational study
Brief summary
The aim of this post-marketing observational study (PMOS) is to provide data on the effectiveness and tolerability of Tarka in patients with a high risk of developing diabetes mellitus, as prescribed by the physicians in a community setting and in accordance with the terms of the local marketing authorization. The following specific questions will be addressed: * Effectiveness of Tarka in lowering the blood pressure in hypertensive patients being at high risk of developing diabetes, not controlled on single-drug therapy. * Tolerability of Tarka as assessed by withdrawal rates.
Detailed description
This is a non-interventional, observational, open-label, multicountry, multicenter post-marketing study in which Tarka is prescribed in the usual manner in accordance with the terms of the local market authorization with regards to dose, population and indication. Patients with a high risk of developing diabetes mellitus treated by secondary care specialists (such as internal medicine specialists, nephrologists, endocrinologists, etc.), whose hypertension is not controlled on single-drug therapy will be included. The assignment of the patient to the treatment with Tarka is not decided in advance by this protocol but falls within current practice. The prescription of Tarka is clearly separated from the decision to include the patient in this study. No additional procedures (other than standard of care) shall be applied to the patients. Each patient will be treated at the physician's discretion. Dosing schedule should be in the accordance with the locally approved Summary of Product Characteristics (SmPC). Physicians will be provided with a study kit that includes a protocol, Tarka's locally approved SmPC, and case reports forms for each patient to be enrolled. The patient's demographic data, height, weight and waist circumference will be reported in the Inclusion visit. The previous antihypertensive therapy should be noted (generic name of the drug and total daily dose). All other drugs the patient currently receives for cardiovascular disease treatment should be recorded as well. The patient will then be followed via regular office visits as determined by the physician. As this study is observational in nature, patient follow-up is not interventional and is left to the judgment of each physician within the 6-month period, which defines the survey for each patient. For indicative purposes, follow-up of participant should enable 3 patient visits during this period. For these reasons, the most likely visits are defined as Inclusion visit at which treatment with Tarka is to be commenced, and then Follow-up visit Month 3 and Follow-up visit Month 6, although dates will depend only on the decision of the physician. As a result, failure to meet these suggested dates will not constitute a breach of the protocol.
Interventions
None listed
Sponsors
Abbott
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients of either gender (more than 18 years of age), with established diagnosis of essential hypertension (systolic blood pressure/ diastolic blood pressure greater than 140/90 mmHg) * Patients not controlled on single-drug therapy and decision was made to introduce Tarka * Patients with a high risk of developing diabetes mellitus (defined according British Medical Society guidelines) with at least one of the following symptoms: * Positive family history of diabetes or * Obesity defined by a Body Mass Index (BMI) greater than 30 kg/m\^2 or a waist circumference greater than 102 cm (males) or greater than 88 cm (females) or * Impaired fasting plasma glucose (FPG) levels of 6.1 to 7.0 mmol/l (100-126 mg/dl)
Exclusion criteria
* Patients with known or established Type 2 diabetes mellitus * The use of Tarka is contraindicated in the following patients: * Hypersensitive to the active substances or to any of the inactive ingredients * With cardiogenic shock * With second and third degree atrioventricular block - except in patients with a functioning artificial pacemaker * With sick sinus syndrome - except in patients with a functioning artificial pacemaker * With atrial fibrillation/flutter and concomitant Wolff-Parkinson-White syndrome * With existing history of angioedema associated with administration of an angiotensin-converting enzyme (ACE) inhibitor * With severe renal or severe liver impairment * In pregnant women (women of childbearing potential who are unwilling to use contraception should not be included) * Lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to Study End | Baseline to 6 months/study end | Participants were to be followed for 6 months. Changes in systolic and diastolic blood pressure were assessed by comparing the blood pressure measurements obtained at the end of Tarka treatment (approximately 6 months) to baseline values. For this analysis of effectiveness the last available value was considered the analysis time point end of study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | 6 months | The percentages of participants achieving and not achieving the target blood pressure of less than 140/90 mmHg at the end of the study are presented. Percentages of participants taking Tarka only or taking Tarka plus another antihypertensive drug are summarized by type of drug: beta blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, diuretics, and angiotensin II (AT-II) receptor antagonists. Participants taking drugs that did not fit any of the above groups (Other), unknown drugs (Unknown), or more than one additional antihypertensive agent are also summarized. |
| Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | 6 months | The number of AEs leading to Tarka discontinuation are summarized. AEs that were considered by the investigator to be possibly or probably related to Tarka are summarized by the severity of the AE (classified as mild, moderate, or severe). AEs considered possibly or probably related to Tarka that led to the discontinuation of Tarka are also presented by severity. |
Countries
Bulgaria, Czechia, Romania, Russia, Slovakia, Slovenia, Ukraine
Participant flow
Pre-assignment details
15,873 participants enrolled in the study. Of these, documentation was available for 15,436 participants. 743 participants were excluded for the following reasons: No Tarka therapy documentation (739) and no follow-up data provided (4), leaving a study population of 14,693. No group assignments were made as the study design was observational.
Participants by arm
| Arm | Count |
|---|---|
| Tarka Therapy Tarka (trandolapril/verapamil hydrochloride) was to be prescribed in a routine manner according to the terms of local regulatory authorizations. Eligible participants had a high risk of developing diabetes mellitus and high blood pressure that was not controlled with a single medication. Participants were to be treated by secondary care specialists such as internal medicine specialists, nephrologists, and endocrinologists. | 14,693 |
| Total | 14,693 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 157 |
| Overall Study | Financial Reasons | 15 |
| Overall Study | Improved Status of Participant | 4 |
| Overall Study | Lack of Effectiveness | 12 |
| Overall Study | No Documentation Available | 437 |
| Overall Study | No Documentation of Tarka Therapy | 739 |
| Overall Study | No Follow-up Documentation Available | 4 |
| Overall Study | Non-compliance | 2 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Reason Unknown | 39 |
| Overall Study | Withdrawal by Subject | 18 |
Baseline characteristics
| Characteristic | Tarka Therapy |
|---|---|
| Age Continuous | 57.8 years STANDARD_DEVIATION 11.5 |
| Age, Customized 18 years of age or younger | 2 participants |
| Age, Customized 65 and older | 4085 participants |
| Age, Customized Age not reported | 41 participants |
| Age, Customized Over 18 and less than 65 | 10565 participants |
| Body Mass Index | 30.0 kg/m^2 STANDARD_DEVIATION 4.8 |
| Body Weight | 87.1 kg STANDARD_DEVIATION 15.2 |
| Region of Enrollment Bulgaria | 309 participants |
| Region of Enrollment Czech Republic | 5643 participants |
| Region of Enrollment Romania | 1251 participants |
| Region of Enrollment Russian Federation | 2085 participants |
| Region of Enrollment Slovakia | 3179 participants |
| Region of Enrollment Slovenia | 1238 participants |
| Region of Enrollment Ukraine | 988 participants |
| Risk Factors for Developing Diabetes Diabetes | 288 participants |
| Risk Factors for Developing Diabetes Impaired Fasting Glucose (IFG) | 506 participants |
| Risk Factors for Developing Diabetes Obesity | 3661 participants |
| Risk Factors for Developing Diabetes Obesity and IFG | 1344 participants |
| Risk Factors for Developing Diabetes Positive Family History and IFG | 563 participants |
| Risk Factors for Developing Diabetes Positive Family History and Obesity | 2983 participants |
| Risk Factors for Developing Diabetes Positive Family History, Obesity, and IFG | 1091 participants |
| Risk Factors for Developing Diabetes Positive Family History of Diabetes | 2891 participants |
| Risk Factors for Developing Diabetes Risk factors not reported | 1366 participants |
| Sex/Gender, Customized Female | 7559 participants |
| Sex/Gender, Customized Gender not reported | 100 participants |
| Sex/Gender, Customized Male | 7034 participants |
| Time Since Diagnosis of Essential Hypertension 10 years or more | 4153 participants |
| Time Since Diagnosis of Essential Hypertension At study inclusion | 249 participants |
| Time Since Diagnosis of Essential Hypertension Between 1 and 2 years | 1536 participants |
| Time Since Diagnosis of Essential Hypertension Between 2 and 3 years | 1573 participants |
| Time Since Diagnosis of Essential Hypertension Between 3 and 5 years | 2482 participants |
| Time Since Diagnosis of Essential Hypertension Between 5 and 10 years | 4187 participants |
| Time Since Diagnosis of Essential Hypertension Less than 1 year | 108 participants |
| Time Since Diagnosis of Essential Hypertension Time since diagnosis not reported | 405 participants |
| Waist Circumference | 97.8 cm STANDARD_DEVIATION 13.1 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15,873 |
| serious Total, serious adverse events | 16 / 14,693 |
Outcome results
Primary
Reduction in Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to Study End
Participants were to be followed for 6 months. Changes in systolic and diastolic blood pressure were assessed by comparing the blood pressure measurements obtained at the end of Tarka treatment (approximately 6 months) to baseline values. For this analysis of effectiveness the last available value was considered the analysis time point end of study.
Time frame: Baseline to 6 months/study end
Population: 2122 participants were excluded from this analysis for the following reasons: age less than 18 years (1), no diagnosis of hypertension (18), not at risk for diabetes (1650), no follow-up blood pressure values (48), no baseline blood pressure values (360), and started Tarka at/after first follow-up visit (45).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tarka Therapy | Reduction in Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to Study End | Systolic blood pressure change from baseline | -28.5 mmHg | Standard Deviation 14.8 |
| Tarka Therapy | Reduction in Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to Study End | Diastolic blood pressure change from baseline | -16.1 mmHg | Standard Deviation 9.5 |
Secondary
Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity
The number of AEs leading to Tarka discontinuation are summarized. AEs that were considered by the investigator to be possibly or probably related to Tarka are summarized by the severity of the AE (classified as mild, moderate, or severe). AEs considered possibly or probably related to Tarka that led to the discontinuation of Tarka are also presented by severity.
Time frame: 6 months
Population: This analysis used the safety analysis population, which included any participant who took at least one dose of Tarka and had at least one follow-up visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | Any AE that led to discontinuation (d/c) of Tarka | 224 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | AEs possibly or probably related to Tarka | 199 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | a) Severity: Mild | 107 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | b) Severity: Moderate | 82 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | c) Severity: Severe | 5 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | d) Severity: Unknown | 5 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | Any AE possibly/probably related that led to d/c | 171 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | a) Severity: Mild | 85 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | b) Severity: Moderate | 79 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | c) Severity: Severe | 5 Events |
| Tarka Therapy | Evaluation of Adverse Events (AEs) Leading to Discontinuation of Tarka and a Summary of All AEs Possibly or Probably Related to Tarka by Frequency and Severity | d) Severity: Unknown | 2 Events |
Secondary
Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka.
The percentages of participants achieving and not achieving the target blood pressure of less than 140/90 mmHg at the end of the study are presented. Percentages of participants taking Tarka only or taking Tarka plus another antihypertensive drug are summarized by type of drug: beta blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, diuretics, and angiotensin II (AT-II) receptor antagonists. Participants taking drugs that did not fit any of the above groups (Other), unknown drugs (Unknown), or more than one additional antihypertensive agent are also summarized.
Time frame: 6 months
Population: 2122 participants were excluded from the analysis for the following reasons: age less than 18 years (1), no diagnosis of hypertension (18), not at risk for diabetes (1650), no follow-up blood pressure values (48), no baseline blood pressure values (360), and started Tarka at/after first follow-up visit (45).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Did not achieve target blood pressure | 31.9 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Achieved target blood pressure | 68.1 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka only | 74.6 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and 1 antihypertensive drug | 20.5 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and a beta blocking agent | 1.1 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and an ACE-inhibitor | 1.4 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and a calcium antagonist | 0.9 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and a diuretic | 10.7 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and an AT-II receptor antagonist | 0.8 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and 1 Other antihypertensive drug | 4.2 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and an Unknown antihypertensive drug | 1.3 Percentage of participants |
| Tarka Therapy | Percentage of Participants Achieving Target Blood Pressure (Less Than 140/90) at Study End and the Need for Other Antihypertensive Drugs, Clustered by Type(s) of Drugs Added to Tarka. | Taking Tarka and more than 1 antihypertensive drug | 4.9 Percentage of participants |