Trial Outcomes & Findings for Effectiveness and Tolerability of Tarka® in the Treatment of Hypertensive Patients With High Risk of Developing Diabetes Mellitus (NCT NCT01079195)

Last Updated: 2011-05-09

Results Overview

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".

Recruitment status

COMPLETED

Target enrollment

15436 participants

Primary outcome timeframe

Baseline to 6 months/study end

Results posted on

2011-05-09

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	15873
Overall Study COMPLETED	14442
Overall Study NOT COMPLETED	1431

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study No Documentation of Tarka Therapy	739
Overall Study No Documentation Available	437
Overall Study Adverse Event	157
Overall Study Reason Unknown	39
Overall Study Withdrawal by Subject	18
Overall Study Financial Reasons	15
Overall Study Lack of Effectiveness	12
Overall Study Physician Decision	4
Overall Study Improved Status of Participant	4
Overall Study No Follow-up Documentation Available	4
Overall Study Non-compliance	2

Baseline Characteristics

Effectiveness and Tolerability of Tarka® in the Treatment of Hypertensive Patients With High Risk of Developing Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tarka Therapy n=14693 Participants 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.
Age Continuous	57.8 years STANDARD_DEVIATION 11.5 • n=5 Participants
Age, Customized 18 years of age or younger	2 participants n=5 Participants
Age, Customized Over 18 and less than 65	10565 participants n=5 Participants
Age, Customized 65 and older	4085 participants n=5 Participants
Age, Customized Age not reported	41 participants n=5 Participants
Sex/Gender, Customized Female	7559 participants n=5 Participants
Sex/Gender, Customized Male	7034 participants n=5 Participants
Sex/Gender, Customized Gender not reported	100 participants n=5 Participants
Region of Enrollment Bulgaria	309 participants n=5 Participants
Region of Enrollment Czech Republic	5643 participants n=5 Participants
Region of Enrollment Romania	1251 participants n=5 Participants
Region of Enrollment Russian Federation	2085 participants n=5 Participants
Region of Enrollment Slovakia	3179 participants n=5 Participants
Region of Enrollment Slovenia	1238 participants n=5 Participants
Region of Enrollment Ukraine	988 participants n=5 Participants
Time Since Diagnosis of Essential Hypertension At study inclusion	249 participants n=5 Participants
Time Since Diagnosis of Essential Hypertension Less than 1 year	108 participants n=5 Participants
Time Since Diagnosis of Essential Hypertension Between 1 and 2 years	1536 participants n=5 Participants
Time Since Diagnosis of Essential Hypertension Between 2 and 3 years	1573 participants n=5 Participants
Time Since Diagnosis of Essential Hypertension Between 3 and 5 years	2482 participants n=5 Participants
Time Since Diagnosis of Essential Hypertension Between 5 and 10 years	4187 participants n=5 Participants
Time Since Diagnosis of Essential Hypertension 10 years or more	4153 participants n=5 Participants
Time Since Diagnosis of Essential Hypertension Time since diagnosis not reported	405 participants n=5 Participants
Risk Factors for Developing Diabetes Positive Family History of Diabetes	2891 participants n=5 Participants
Risk Factors for Developing Diabetes Obesity	3661 participants n=5 Participants
Risk Factors for Developing Diabetes Impaired Fasting Glucose (IFG)	506 participants n=5 Participants
Risk Factors for Developing Diabetes Positive Family History and Obesity	2983 participants n=5 Participants
Risk Factors for Developing Diabetes Positive Family History and IFG	563 participants n=5 Participants
Risk Factors for Developing Diabetes Obesity and IFG	1344 participants n=5 Participants
Risk Factors for Developing Diabetes Positive Family History, Obesity, and IFG	1091 participants n=5 Participants
Risk Factors for Developing Diabetes Diabetes	288 participants n=5 Participants
Risk Factors for Developing Diabetes Risk factors not reported	1366 participants n=5 Participants
Body Mass Index	30.0 kg/m^2 STANDARD_DEVIATION 4.8 • n=5 Participants
Body Weight	87.1 kg STANDARD_DEVIATION 15.2 • n=5 Participants
Waist Circumference	97.8 cm STANDARD_DEVIATION 13.1 • n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Tarka Therapy n=12571 Participants 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.
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
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 outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Tarka Therapy n=12571 Participants 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.
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
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
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
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
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
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
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
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
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
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
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
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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tarka Therapy n=14693 Participants 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.
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
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
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
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
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
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
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

Adverse Events

Tarka Therapy

Serious events: 16 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tarka Therapy n=15873 participants at risk；n=14693 participants at risk 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.
Cardiac disorders Atrial fibrillation	0.01% 2/14693 • Number of events 2 • 6 months
Cardiac disorders Cardiac failure	0.01% 1/14693 • Number of events 1 • 6 months
Cardiac disorders Myocardial infarction	0.01% 2/14693 • Number of events 2 • 6 months
Cardiac disorders Myocardial ischaemia	0.01% 1/14693 • Number of events 1 • 6 months
General disorders Asthenia	0.01% 1/14693 • Number of events 1 • 6 months
General disorders Death	0.07% 11/14693 • Number of events 11 • 6 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.01% 1/14693 • Number of events 1 • 6 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.01% 1/14693 • Number of events 1 • 6 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.01% 1/14693 • Number of events 1 • 6 months
Psychiatric disorders Alcohol abuse	0.01% 1/14693 • Number of events 1 • 6 months
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.01% 1/14693 • Number of events 1 • 6 months

Other adverse events

Adverse event data not reported

Additional Information

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