Clinical trial NCT00162955: Prevention of CHOP-induced Chronic Cardiotoxicity
Official title: The Multi-centers Trial for Patients With Non-Hodgkin's Lymphoma to Assess the Protective Effect of Valsartan on Chronic Cardiotoxicity Induced by CHOP
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non-Hodgkin's Lymphoma
Keywords: untreated adult Non-Hodgkin's Lymphoma
CHOP protocol
Angiotensin II Type 1 Receptor Blockers
Cardiomyopathy
Lead sponsor: Osaka City University
Sponsor class: OTHER
First posted: 2005-09-13
Enrollment: 150
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Cardiac Event after 3rd and 6th course of CHOP(-R)
timeFrame: Basically 14-21 (at a maximum 28) days after the start of 3rd and 6th course of CHOP(-R).
Secondary outcomes:
measure: Changes of ECG, UCG and serum markers after 3 and 6 courses of CHOP (-R)
timeFrame: 14-21 (at a maximum 28) days after the start of 3rd and 6th course of CHOP(-R).
Other outcomes:
Locations:
city: Osaka
country: Japan
facility: Graduate School of Medicine, Osaka City University
Study officials:
affiliation: Graduate School of Medicine, Osaka City University
name: Masayuki Hino, MD, PhD
role: STUDY_CHAIR
affiliation: Graduate School of Medicine, Osaka City University
name: Hirohisa Nakamae, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Toko H, Oka T, Zou Y, Sakamoto M, Mizukami M, Sano M, Yamamoto R, Sugaya T, Komuro I. Angiotensin II type 1a receptor mediates doxorubicin-induced cardiomyopathy. Hypertens Res. 2002 Jul;25(4):597-603. doi: 10.1291/hypres.25.597.