Effects of Valsartan and Aliskiren on Hemostatic Indices in Hypertensive Diabetics
Information source: HeartDrug Research LLC
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus
Intervention: Aliskiren + Valsartan (Drug)
Phase: Phase 4
Status: Active, not recruiting
Sponsored by: HeartDrug Research LLC Official(s) and/or principal investigator(s): Victor Serebruany, MD, PhD, Study Director, Affiliation: HeartDrug Research LLC
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.
Clinical Details
Official title: A Randomized Evaluation of the Effects of Valsartan and Aliskiren in Combination Versus Tekturna Alone on Hemostatic Biomarkers in Patients With Newly Diagnosed Mild to Moderate Hypertension and Type 2 Diabetes Mellitus
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment
Primary outcome: 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.
Secondary outcome: 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).
Detailed description:
Objectives:
There are 2 objectives in the index study. • The primary objective is to determine how
therapy with valsartan (160mg/daily) in combination with aliskiren (150-300mg/daily) over
four weeks affects platelet/coagulation/fibrinolytic biomarkers in recently diagnosed
hypertensive patients with type 2 diabetes mellitus. However, this is an exploratory study,
our current knowledge is based on in vitro and ex vivo evidence for valsartan, but only on
in vitro aliskiren data. There are no data on antithrombotic biomarkers currently available
for the combination therapy.
The secondary objective is:
• To define 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).
Study Design:
This is a randomized 1: 1, two arm, single-blind, single-site, parallel group, post-marketing
comparison study of the effects on antithrombotic biomarkers of aliskiren 150-300mg/day
alone vs combined treatment with aliskiren 150-300mg/day plus valsartan 160mg/day over a
four week primary treatment period. An optional four week extension phase may be offered
pending assessment of the antithrombotic biomarker assays at week four.
Population:
Two groups (25 patients each), for a total of 50, recently diagnosed hypertensive patients
with previously diagnosed 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.
Eligibility
Minimum age: 21 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. 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).
2. Adults between 21 - 65 years old
3. 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.
4. 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.
5. Aspirin 81 mg/daily
6. Signed informed consent
7. Must maintain same diet/exercise regimen
Exclusion Criteria:
1. Thrombolytic therapy, GP IIb/IIIa inhibitor, thienopyridines, antifibrinolytics, COX-
inhibitors, prostacyclin analogues, and vitamin K antagonists within 30 days of
enrollment
2. Platelet count < 100,000/microL
3. History of bleeding disorder
4. Hct < 30%, serum creatinine ≥3 mg/dL, liver impairment defined as ALT/AST > 3 times
upper limit of normal.
5. Glomerular filtration rate <60ml/min/1. 73m2
6. Patients currently treated with any antiplatelet agent other than aspirin 81 mg/day
7. Admission for acute vascular syndrome (unstable angina, MI, stroke),
revascularization procedure with stent placement, or other major
coronary/cerebrovascular event within 30 days.
8. Active participation in other investigational drug or device trial within the last 30
days.
9. Allergy or intolerance to any of the study medications.
10. Congestive Heart Failure (NYHA I-IV)
11. Malignancies except treated non-melanoma superficial skin cancers
12. Acute infections
13. Type I diabetes, Cushings syndrome, or pancreatic deficiency due to malignancy or
systemic disease
14. Insulin therapy, sulfonylureas, thiazolidinediones,meglitinides, D-phenylalanine
derivatives, amylin synthetic derivatives, and incretin mimetics.
15. 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.
16. Age over 65 years
17. History of cigarette smoking within past 10 years
Locations and Contacts
Dr. Pokov's Polyclinic. 6821 Reisterstown Road Suite 206, Baltimore, Maryland 21215, United States
Additional Information
Review Board Core laboratory facility
Starting date: March 2010
Last updated: March 29, 2010
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