CLINICAL TRIALS PROFILE FOR TRANDOLAPRIL; VERAPAMIL HYDROCHLORIDE

All Clinical Trials for trandolapril; verapamil hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00497666 ↗	Association Between Rosiglitazone Use and Clinical Course of Diabetic Nephropathy: Population-Based Study	Unknown status	Assaf-Harofeh Medical Center		2007-08-01	Recent data show that Rosiglitazone treatment can reduce proteinuria in diabetic patients. However, currently there are no trials that examine the effects of Rosiglitazone on kidney disease progression, that is, doubling of serum creatinine or time to onset of end-stage renal disease, in patients with diabetic nephropathy. We decided to study retrospectively the possible association between rosiglitazone use and clinical course of diabetic nephropathy, including rate of deterioration of renal function, appearance and progression of microalbuminuria/proteinuria, survival and acceptance to renal replacement therapy.
NCT00503152 ↗	Preventing Microalbuminuria in Type 2 Diabetes	Completed	Agenzia Italiana del Farmaco	Phase 3	2007-05-01	In people with type 2 diabetes, microalbuminuria is a strong, independent risk factor for diabetic nephropathy and cardiovascular morbidity and mortality. ACE inhibitor therapy decreased the risk of microalbuminuria in hypertensive subjects with type 2 diabetes and normoalbuminuria by about 40%. Available data suggest that angiotensin II receptor blockers (ARBs) might have a similar renoprotective effect and that this effect might be increased by combined ACE inhibitor therapy. The study will evaluate the effects, at similar blood pressure control (systolic/diastolic <130/80 mmHg), for a period of three years, of dual renin-angiotensin-system (RAS) blockade by benazepril and valsartan combination therapy as compared to single RAS blockade by benazepril or valsartan alone on microalbuminuria and cardiovascular events in high-risk patients with type 2 diabetes, creatinine <1.5 mg/dl, no evidence of microalbuminuria but at high risk of renal disease, with hypertension and a urinary albumin excretion between 7 and 19 microgram/min. The relationship between albuminuria and cardiovascular outcomes will also be evaluated. The study is expected to show a more effective prevention of microalbuminuria and cardiovascular events with combined than with single drug ACE inhibitor or ARB therapy. As compared to ACE inhibitor, ARB therapy is expected to have a similar effect on microalbuminuria, but an inferior cardioprotective effect. Applied to clinical practice, the findings should help preventing renal and cardiovascular complications, and related treatment costs, of type 2 diabetes.
NCT00503152 ↗	Preventing Microalbuminuria in Type 2 Diabetes	Completed	Mario Negri Institute for Pharmacological Research	Phase 3	2007-05-01	In people with type 2 diabetes, microalbuminuria is a strong, independent risk factor for diabetic nephropathy and cardiovascular morbidity and mortality. ACE inhibitor therapy decreased the risk of microalbuminuria in hypertensive subjects with type 2 diabetes and normoalbuminuria by about 40%. Available data suggest that angiotensin II receptor blockers (ARBs) might have a similar renoprotective effect and that this effect might be increased by combined ACE inhibitor therapy. The study will evaluate the effects, at similar blood pressure control (systolic/diastolic <130/80 mmHg), for a period of three years, of dual renin-angiotensin-system (RAS) blockade by benazepril and valsartan combination therapy as compared to single RAS blockade by benazepril or valsartan alone on microalbuminuria and cardiovascular events in high-risk patients with type 2 diabetes, creatinine <1.5 mg/dl, no evidence of microalbuminuria but at high risk of renal disease, with hypertension and a urinary albumin excretion between 7 and 19 microgram/min. The relationship between albuminuria and cardiovascular outcomes will also be evaluated. The study is expected to show a more effective prevention of microalbuminuria and cardiovascular events with combined than with single drug ACE inhibitor or ARB therapy. As compared to ACE inhibitor, ARB therapy is expected to have a similar effect on microalbuminuria, but an inferior cardioprotective effect. Applied to clinical practice, the findings should help preventing renal and cardiovascular complications, and related treatment costs, of type 2 diabetes.
NCT00234871 ↗	Tarka® vs. Lotrel® in Hypertensive, Diabetic Subjects With Renal Disease (TANDEM)	Completed	Abbott	Phase 4	2004-01-01	The primary objective of this study is to determine if trandolapril/verapamil (Tarka®) is superior to amlodipine/benazepril (Lotrel®) in reduction of albuminuria in hypertensive subjects with Type 2 diabetes mellitus (DM) and diabetic nephropathy
NCT00133692 ↗	INVEST: INternational VErapamil SR Trandolapril STudy	Completed	Abbott	Phase 4	1997-09-01	Because blood pressure affects the heart, blood vessels, kidneys, and the entire body, it is important to keep it as normal as possible. There are several different ways to control blood pressure and to prevent or limit the development of heart disease due to high blood pressure. The purpose of this study is to compare two treatments to see how well they work and the difference in their side effects. One treatment includes the use of a calcium antagonist drug (Isoptin sustained release [SR] or Verapamil SR). The other treatment excludes the calcium antagonist and may include a non-calcium antagonist drug called a beta blocker (Tenormin or Atenolol). Both treatments may also include medication called angiotensin converting enzyme (ACE) inhibitors and water pills. None of the drugs in this study are experimental, they are all approved by the Food and Drug Administration (FDA).
NCT00133692 ↗	INVEST: INternational VErapamil SR Trandolapril STudy	Completed	University of Florida	Phase 4	1997-09-01	Because blood pressure affects the heart, blood vessels, kidneys, and the entire body, it is important to keep it as normal as possible. There are several different ways to control blood pressure and to prevent or limit the development of heart disease due to high blood pressure. The purpose of this study is to compare two treatments to see how well they work and the difference in their side effects. One treatment includes the use of a calcium antagonist drug (Isoptin sustained release [SR] or Verapamil SR). The other treatment excludes the calcium antagonist and may include a non-calcium antagonist drug called a beta blocker (Tenormin or Atenolol). Both treatments may also include medication called angiotensin converting enzyme (ACE) inhibitors and water pills. None of the drugs in this study are experimental, they are all approved by the Food and Drug Administration (FDA).

Clinical Trial Conditions for trandolapril; verapamil hydrochloride

Condition Name

Condition Name for trandolapril; verapamil hydrochloride
Intervention	Trials
Diabetes	4
Hypertension	2
Coronary Artery Disease	1
Diabetic Nephropathy	1

Condition MeSH

Condition MeSH for trandolapril; verapamil hydrochloride
Intervention	Trials
Hypertension	3
Diabetes Mellitus	2
Coronary Disease	1
Coronary Artery Disease	1

Clinical Trial Locations for trandolapril; verapamil hydrochloride

Trials by Country

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Trials by Country for trandolapril; verapamil hydrochloride
Location	Trials
Italy	3
Israel	1
United States	1
China	1

Trials by US State

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−

Trials by US State for trandolapril; verapamil hydrochloride
Location	Trials
Florida	1

Clinical Trial Progress for trandolapril; verapamil hydrochloride

Clinical Trial Phase

Clinical Trial Phase for trandolapril; verapamil hydrochloride
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	1

Clinical Trial Status

Clinical Trial Status for trandolapril; verapamil hydrochloride
Clinical Trial Phase	Trials
Completed	3
Unknown status	2

Clinical Trial Sponsors for trandolapril; verapamil hydrochloride

Sponsor Name

Sponsor Name for trandolapril; verapamil hydrochloride
Sponsor	Trials
Abbott	2
University of Florida	1
Assaf-Harofeh Medical Center	1

Sponsor Type

Sponsor Type for trandolapril; verapamil hydrochloride
Sponsor	Trials
Other	5
Industry	2

Clinical Trials, Market Analysis, and Projections for Trandolapril and Verapamil Hydrochloride

Introduction

Trandolapril and verapamil hydrochloride are two medications that have been extensively studied and used in the management of various cardiovascular conditions. This article will delve into the key clinical trials, market analysis, and future projections for these drugs, particularly when used individually and in combination.

Clinical Trials: Trandolapril

TRACE Study

One of the pivotal clinical trials for trandolapril is the Trandolapril Cardiac Evaluation (TRACE) study. This study focused on patients who had survived a myocardial infarction (MI) but had reduced left ventricular function. The trial enrolled 1,749 patients and followed them for a mean of 36 months.

• Key Findings: The study showed that trandolapril significantly reduced the risk of overall mortality, cardiovascular mortality, sudden death, and the development of severe heart failure. The relative risk of death in the trandolapril group was reduced by 22% (risk reduction = 0.78, 95% CI 0.67-0.91; p = 0.001)[1][4].

Patient Populations and Exclusions

The TRACE study included adults with acute MI 2-6 days prior to trial entry and an echocardiographic ejection fraction of less than 35%. Exclusions included absolute or relative contraindications to ACE inhibitors, severe uncontrolled diabetes, hyponatremia, and other significant health conditions[1].

Clinical Trials: Verapamil Hydrochloride

INVEST Study

The International Verapamil-Trandolapril Study (INVEST) compared the efficacy and safety of a calcium antagonist-based blood pressure treatment strategy using verapamil with a beta-blocker-based strategy using atenolol. The study involved over 22,000 patients and showed that both treatment strategies had similar outcomes in terms of survival free from stroke or MI[3].

• Key Findings: The study found no significant difference in the primary endpoint of survival free from stroke or MI between the verapamil and atenolol arms. However, it highlighted the effectiveness of verapamil in managing hypertension, especially when combined with other medications like trandolapril[3].

Combination Therapy: Trandolapril and Verapamil Hydrochloride

TARKA Studies

The combination of trandolapril and verapamil hydrochloride, known as TARKA, has been studied in several clinical trials. These studies have shown that the combination therapy offers an additive antihypertensive effect compared to monotherapy with either drug.

• Key Findings: Clinical trials demonstrated that TARKA significantly reduced blood pressure, with reductions in systolic and diastolic blood pressure being greater than those achieved with verapamil alone. The combination was also found to be safe, with adverse events similar to those of the individual components[2][5].

Market Analysis

Current Market Position

Trandolapril and verapamil hydrochloride, both individually and in combination, are well-established in the market for treating hypertension and other cardiovascular conditions. The combination product, TARKA, is particularly popular due to its additive antihypertensive effects and once-daily dosing convenience.

• Market Share: The market share of these drugs is significant, especially in the segment of cardiovascular medications. The combination therapy has carved out a niche by offering a comprehensive approach to blood pressure management[5].

Competitive Landscape

The market for cardiovascular medications is highly competitive, with numerous ACE inhibitors and calcium channel blockers available. However, trandolapril and verapamil hydrochloride have maintained their position due to their proven efficacy and safety profiles.

• Competitors: Other ACE inhibitors like lisinopril and enalapril, and calcium channel blockers like amlodipine, compete in the same market space. However, the unique combination of trandolapril and verapamil hydrochloride offers a distinct advantage[5].

Projections and Future Outlook

Growing Demand for Cardiovascular Medications

The global demand for cardiovascular medications is expected to grow due to increasing prevalence of hypertension, heart failure, and other cardiovascular diseases.

• Market Growth: The market for cardiovascular drugs is projected to expand, driven by an aging population and rising incidence of cardiovascular conditions. This trend is expected to benefit trandolapril and verapamil hydrochloride, both individually and in combination[5].

Innovations and New Indications

Future research may explore new indications for trandolapril and verapamil hydrochloride, such as prevention of proteinuria in high-risk patients, which could further expand their market potential.

• New Indications: Studies have already shown that trandolapril reduces the progression to proteinuria in high-risk patients. Expanding these indications could increase the market share of these drugs[4].

Key Takeaways

• Clinical Efficacy: Trandolapril has been shown to significantly reduce mortality and cardiovascular events in patients with reduced left ventricular function post-MI.
• Combination Therapy: The combination of trandolapril and verapamil hydrochloride offers additive antihypertensive effects and is safe for use.
• Market Position: These drugs are well-established in the market, with a significant market share in the cardiovascular segment.
• Future Outlook: The growing demand for cardiovascular medications and potential new indications are expected to drive market growth.

FAQs

What is the primary use of trandolapril in clinical practice?

Trandolapril is primarily used to reduce the risk of overall mortality, cardiovascular mortality, and the development of severe heart failure in patients with reduced left ventricular function after a myocardial infarction.

How does the combination of trandolapril and verapamil hydrochloride compare to monotherapy?

The combination of trandolapril and verapamil hydrochloride offers an additive antihypertensive effect compared to monotherapy with either drug, providing greater blood pressure reductions.

What are the common adverse events associated with TARKA?

The most frequently observed adverse events with TARKA are headache and cough, which are well-known side effects of the individual components.

Can trandolapril be used in patients with diabetes?

Yes, trandolapril is particularly beneficial in patients with diabetes mellitus by reducing the risk of progression to severe heart failure and saving lives.

How does food intake affect the bioavailability of TARKA?

Food intake does not alter the bioavailability of trandolapril but decreases the bioavailability of verapamil by 37% and delays its peak plasma concentration by approximately 7 hours.

Sources

1. The Trandolapril Cardiac Evaluation TRACE Study - American College of Cardiology.
2. Public Assessment Report - Cbg-meb.
3. International Verapamil-Trandolapril Study - INVEST - American College of Cardiology.
4. Update on the use of trandolapril in the management of cardiovascular disorders - Vasc Health Risk Manag.
5. TARKA® (trandolapril/verapamil hydrochloride ER tablets) - FDA.