Prevention of CHOP-induced Chronic Cardiotoxicity

Study Overview
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Brief Summary
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The purpose of this study is to assess the protective effect of Valsartan on chronic cardiotoxicity induced by CHOP.

Detailed Description
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Doxorubicin has been one of the most important key drugs in treatment for malignancies. However, its use is limited by dose-dependent cumulative cardiotoxicity. This multi-centers trial was designed to investigate the preventive effect of Valsartan, the angiotensin II type 1 receptor blocker (ARB) on chronic cardiotoxicity due to doxorubicin based chemotherapy. Patients with untreated non-Hodgkin's lymphoma who are scheduled to receive at least 6 courses of the standard CHOP (-R) will be randomized by the minimization methods to the treatment group with Valsartan (80mg once daily by oral during entire 6 courses of CHOP) or control group. Cardiac function will be evaluated in detail before and after 3 and 6 courses of CHOP (-R).

Official Title
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The Multi-centers Trial for Patients With Non-Hodgkin's Lymphoma to Assess the Protective Effect of Valsartan on Chronic Cardiotoxicity Induced by CHOP

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Valsartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of non-Hodgkin's lymphoma (NHL) Untreated lymphoma Performance status from 0 to 1, Total serum bilirubin < 2.0 mg/dl Serum creatinine level < 2.0 mg/dl Ejection fraction of the left ventricle >50 % Systolic blood pressure at rest being 90 mmHg or more Exclusion Criteria: Severe complication including chronic or acute heart failure, angina, old myocardial infarction, liver cirrhosis, and interstitial pneumonia Pregnancy, nursing mothers or women of child-bearing potential Hypertension under medication Diabetes mellitus under medication Hyperthyroidism, nephrotic syndrome, Cushing's syndrome Atrial arrythmias Severe psychopathy Cerebrovascular accidents within the past 3 months Positive serum HBs antigen or HCV antibody A history of renal failure A contraindication to A-II antagonists or noncompliance Treatment with any of the following drugs within the past 3 months : A-II antagonists, ACE inhibitors, vitamin E, probucol, calcium antagonists, beta-blockers, and steroid pulse therapy.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARB administration<br>80mg/day from the day of the start of 1st CHOP until the completion of all the evaluations | Drug: Valsartan<br>* Patients allocated into ARB administration group take Valsartan (80mg/day) from the day of the start of 1st CHOP until the completion of all the evaluations.<br>* Other names: Diovan;|
| No Intervention: non-administration<br>ARB non-administration group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Event after 3rd and 6th course of CHOP(-R) |  | Basically 14-21 (at a maximum 28) days after the start of 3rd and 6th course of CHOP(-R). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of ECG, UCG and serum markers after 3 and 6 courses of CHOP (-R) |  | 14-21 (at a maximum 28) days after the start of 3rd and 6th course of CHOP(-R). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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untreated adult Non-Hodgkin's Lymphoma, CHOP protocol, Angiotensin II Type 1 Receptor Blockers, Cardiomyopathy