Effects of Valsartan and Aliskiren on Hemostatic Indices in Hypertensive Diabetics

NCT01095822 | Unknown Phase 4 DMC

• 1 other identifier: DT-NOV-09-37918
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

People with both hypertension and diabetes have a higher chance of developing heart and arterial problems that could be reduced with anti-coagulant therapy. Valsartan (Diovan), an FDA approved angiotensin-II receptor antagonist (blocker) clinically indicated for the treatment of essential hypertension is known to inhibit platelet activity in both an in vitro and ex vivo setting. Aliskiren (Tekturna) is a recently FDA-approved potent direct renin inhibitor which is also an effective anti-hypertensive agent in patients with mild-to-moderate hypertension and which, in vitro, modulates antithrombin III in plasma. Therefore, in addition to being clinically approved anti-hypertensive medications, combining these two agents will potentially target both primary hemostasis (platelets) and anticoagulant (antithrombin-III is a cornerstone substrate for heparin) properties to exert their anti-thrombotic efficacy simultaneously. This combination strategy may not only improve hypertension management, but also improve vascular outcomes in high-risk diabetic population via favorable effects on anti-thrombotic activity. Importantly, there have been no significant additional safety concerns of using the combination of aliskiren and valsartan. The investigators hypothesis is that valsartan 160 mg/daily in combination with aliskiren 150-300 mg/daily for 4 weeks will favorably affect blood levels of platelet/coagulation/fibrinolytic biomarkers (ie, diminish platelet activity, and enhance antithrombin III potency) when compared with monotherapy with aliskiren 150mg/daily in hypertensive patients with type 2 diabetes mellitus.

Conditions

Diabetes Mellitus

Keywords

Diabetes; Hypertension; Platelets; Hemostasis; Aliskiren; Valsartan

Outcome Measures

Primary Outcomes (1)

• How therapy with valsartan (160mg/daily) in combination with aliskiren (150-300mg/daily) affects platelet/coagulation/fibrinolytic biomarkers in recently diagnosed hypertensive patients with type 2 diabetes mellitus.

  4 weeks

Secondary Outcomes (1)

• Whether combination therapy is superior over monotherapy with aliskiren with regard to the improvement of hemostatic biomarkers (platelet aggregation, expression of GP IIb/IIIa, and plasma levels of antithrombin-III).

  4 weeks

Study Arms (2)

Aliskiren

ACTIVE COMPARATOR

25 patients with recently diagnosed hypertension and mild to moderate type 2 diabetes will constitute the proposed study population. The diagnosis of diabetes will be made based on the American Diabetes Association criteria, such as random plasma glucose \>200 mg/dL with or without symptoms of hyperglycemia (polydipsia, polyuria, polyphagia) and weight loss, or fasting plasma glucose \> 126 mg/dL, to be determined at least twice. Patients will qualify if they are insulin-free, treated with an oral antiglycemic agent,(metformin only) and/or managed on diet alone for no less than 30 days and have adequate glucose control at the time of their Screening Visit.

Drug: Aliskiren + Valsartan

Aliskiren + Valsartan

EXPERIMENTAL

25 patients with recently diagnosed hypertension, and mild to moderate type 2 diabetes will constitute the proposed study population. The diagnosis of diabetes will be made based on the American Diabetes Association criteria, such as random plasma glucose \>200 mg/dL with or without symptoms of hyperglycemia (polydipsia, polyuria, polyphagia) and weight loss, or fasting plasma glucose \> 126 mg/dL, to be determined at least twice. Patients will qualify if they are insulin-free, treated with an oral antiglycemic agent,(metformin only) and/or managed on diet alone for no less than 30 days and have adequate glucose control at the time of their Screening Visit.

Drug: Aliskiren + Valsartan

Interventions

Aliskiren + Valsartan DRUG

Comparison of combination (aliskiren + valsartan) therapy versus valsartan alone on hemostatic indices

Aliskiren; Aliskiren + Valsartan

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The diagnosis of Type 2 Diabetes Mellitus will have been determined by the following Criteria, as characterized by recurrent or persistent hyperglycemia, and diagnosed by demonstrating any one of the following.
• Fasting plasma glucose level at or above 126 mg/dL but less than 250 mg/dL on more than one determination.
• Plasma glucose at or above 200 mg/dL two hours after a 75 g oral glucose load as in a glucose tolerance test.
• Symptoms of hyperglycemia and casual plasma glucose at or above 200 mg/dL.
• Glycated hemoglobin (hemoglobin A1C) at or above 6.5 but below 8.5%. (This criterion was recommended by the American Diabetes Association in 2010).
• Adults between 21 - 65 years old
• Have been diagnosed with Type 2 DM according to the criteria listed above, and treated with metformin 1-2 g/daily as their only diabetic medication, and/or an approved ADA diet for no less than 30 days.
• Documented evidence of Stage 1 or Stage 2 essential hypertension as noted below: However, the actual treatment threshold will be left to the discretion of the study investigators.
• Stage 1: systolic 140-159 mmHg and diastolic 90-99 mmHg Stage 2: systolic \>160 mmHg and diastolic \>100 mmHg However, there is accumulated evidence that patients with consistent blood pressures over 130/80 mmHg along with Type 1 or Type 2 diabetes, or kidney disease are at increased risk for progressive morbidity and mortality and require a lower threshold for further treatment.
• Aspirin 81 mg/daily
• Signed informed consent
• Must maintain same diet/exercise regimen

You may not qualify if:

• Thrombolytic therapy, GP IIb/IIIa inhibitor, thienopyridines, antifibrinolytics, COX- inhibitors, prostacyclin analogues, and vitamin K antagonists within 30 days of enrollment
• Platelet count \< 100,000/microL
• History of bleeding disorder
• Hct \< 30%, serum creatinine ≥3 mg/dL, liver impairment defined as ALT/AST \> 3 times upper limit of normal.
• Glomerular filtration rate \<60ml/min/1.73m2
• Patients currently treated with any antiplatelet agent other than aspirin 81 mg/day
• Admission for acute vascular syndrome (unstable angina, MI, stroke), revascularization procedure with stent placement, or other major coronary/cerebrovascular event within 30 days.
• Active participation in other investigational drug or device trial within the last 30 days.
• Allergy or intolerance to any of the study medications.
• Congestive Heart Failure (NYHA I-IV)
• Malignancies except treated non-melanoma superficial skin cancers
• Acute infections
• Type I diabetes, Cushings syndrome, or pancreatic deficiency due to malignancy or systemic disease
• Insulin therapy, sulfonylureas, thiazolidinediones,meglitinides, D-phenylalanine derivatives, amylin synthetic derivatives, and incretin mimetics.
• Pregnancy, confirmed by serum rosette inhibition assay for early pregnancy factor detectable. For women of child-bearing potential (WOCP), continuous abstinence, fertility awareness, hormonal contraceptives, and/or mechanical methods will apply to prevent pregnancy during the entire study duration. Should a subject become pregnant during the study, the anti-hypertensive treatment with either or both study medications will be discontinued immediately by the treating physician/investigator as per FDA warnings regarding potential fetal/neonatal morbidity and mortality.

Sponsors & Collaborators

• HeartDrug Research LLC: lead
• Novartis: collaborator

Study Sites (1)

Dr. Pokov's Polyclinic. 6821 Reisterstown Road Suite 206

Baltimore, Maryland, 21215, United States

Location

Related Links

• Core laboratory facility

MeSH Terms

Conditions

Diabetes Mellitus; Hypertension

Interventions

aliskiren; Valsartan

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Victor Serebruany, MD, PhD

  HeartDrug Research LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: March 30, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: March 1, 2011
• Last Updated: March 30, 2010

Record last verified: 2010-03

Locations

US (1)