Heart and Blood Diseases

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Neoplasms

Heart Failure

Ascites

Liver Cirrhosis

Carcinoma

Fibrosis

Heart Diseases

Liver Diseases

Gastrointestinal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Hematinics

All Drugs and Chemicals

Natriuretic Agents

Liver Extracts

Natriuretic Peptide, Brain

Patients must fulfill Framingham and/or Boston criteria for heart failure and have systolic or diastolic disfunction in rest echocardiography.

Patients must have a biopsy proven diagnosis of liver cirrhosis or the diagnosis established on clinical basis in cases of known etiology of liver disease, peripheral signs of chronic liver disease, esophageal varices at endoscopy and an imaging method with evidence of cirrhosis.

Patients must fulfill stringent diagnostic criteria for the cause of ascites, by clinical criteria, laboratory and imaging tests and histology when appropriate.

Patients must fulfill the aforementioned criteria for both conditions.

BNP, SAAG, ascites total protein, echocardiography

Alberto Q. Farias, MD, PhD

The serum albumin ascites gradient (SAAG) is a recommended tool for ascites diagnosis since values ≥1.1 g/dl are found in nearly 97% of patients with portal hypertension. However, it mislabels chronic liver disease and heart failure as the cause of ascites. Because type-B Natriuretic Peptide (BNP) is increased in several body fluids of patients with both systolic and diastolic dysfunction, it was found to be a useful marker for diagnosing heart failure and pleural effusion due to heart failure. Nevertheless, to date, the performance of BNP testing for assessing the etiology of ascites has not been examined. The current prospective study is aimed at comparing the following strategies for diagnosing heart failure as the cause of ascites: 1) SAAG plus total protein concentration in ascitic fluid (gold standard); 2) SAAG plus BNP concentration in ascitic fluid; 3) SAAG plus BNP concentration in serum; 4) serum BNP concentrations.

SAAG, ascitic fluid protein concentration, serum and ascites type-B Natriuretic Peptide and echocardiography will be performed in all patients. The final diagnosis of the cause of ascites will be adjudicated by independent physicians, blinded for the results of ascitic fluid biochemistry and BNP. Patients will be divided into four groups: Heart failure, Liver cirrhosis, concurrent heart failure and liver cirrhosis (mixed) and other causes of ascites.

Diagnostic criteria for the cause of ascites - two independent cardiologists and two hepatologists will interview and examine the enrolled patients and review the clinical records, laboratory and imaging findings to adjudicate the correct final cause of the ascites. They will have access to all exams that patients undergo, including results of biopsies, laboratory tests, chest radiography, Doppler ultrasound, computerized tomography, magnetic resonance imaging, echocardiography and cardiac catheterism. Liver cirrhosis diagnosis will be biopsy proven or established on clinical basis in patients with known etiology of liver disease, peripheral signs of chronic liver disease, esophageal varices at endoscopy and a compatible imaging method. Heart failure will be diagnosed in patients fulfilling Framingham and/or Boston criteria and by rest echocardiography. Other causes of ascites will be diagnosed by appropriate laboratory and imaging tests and by histology when appropriate.

SAAG, ascitic fluid protein concentration and type-B Natriuretic Peptide - will be assessed in all patients. BNP measurements will be carried out according to the instructions of the manufacturer in fresh samples (ADVIA Centaur BNP Siemens Inc, San Diego, CA, USA). This assay is a fully automated two-site sandwich immunoassay based on chemiluminescent technology, standardized with synthetic purified protein preparation of human BNP (aminoacid 77 to 108), for quantitative BNP within the range of \<2.0 to 5,000 pg/ml. The BNP assay is reliable in presence of increased values of several biochemical parameters usually found in patients with decompensated cirrhosis. No interference in measurement has been reported from urea up to 200 mg/dL, creatinine up to 2.5 mg/dL, unconjugated bilirubin up to 25 mg/dL, conjugated bilirubin up to 25 mg/dL, triglycerides up to 800 mg/dL, cholesterol up to 1000 mg/dL and from commonly used pharmaceutical drugs. For testing in whole blood, a 4 ml sample will be collected in an EDTA containing tube. A 10 ml of ascitic fluid will be collected at the same time by paracentesis before infusion of albumin or volume overload. Laboratory staff will be unaware of both the clinical diagnosis and routine laboratory results.

Echocardiography - will performed at rest in all patients for assessing the following parameters: ejection fraction, left atrium diameter, systolic and diastolic left ventricle diameter and diastolic dysfunction.

Base-line demographical,past medical history and laboratory test results of all patients will be recorded.

B-type Natriuretic Peptide in the Diagnosis of Heart Failure Related Ascites

* ROC curves of different strategies with and without BNP levels for diagnosing heart failure as the cause of ascites.
* Sensitivity, specificity, accuracy, predictive values, likelihood ratios.

University of Sao Paulo General Hospital

University of Sao Paulo

M.D. P.h.D.

Blood and Lymph Conditions

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Syndrome

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Antineoplastic Agents

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

blood sampling before, during and after doxorubicin administration

doxorubicin

Joachim Boos, MD, Prof.

Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity .

* Paediatric patients up to the age of 17 years will be included. Number and time points of PK sampling will depend on age and tumour type.
* PK samples will be collected from two doxorubicin administrations. Analyzing samples from two doxorubicin administrations will allow distinguishing between interindividual, intraindividual and residual variability.
* Doxorubicin and its major metabolite doxorubicinol will be measured in plasma using HPLC
* In addition, the natriuretic peptide BNP and the precursors NT-pro ANP and NT-proBNP as well as troponin T will be measured in plasma up to 28 days after doxorubicin administration to evaluate their use as clinical markers for cardiotoxicity.
* A data set of max 5 samples (3 +2 (in the 1st + 2nd Doxorubicin sampling periods)) will be collected in the younger children (\< 3 years) and a data set of max. 8 samples ( 5 + 3) will be collected in the older children. Samples will be taken at predefined time points/ time intervals.
* An additional DNA sample will be taken and analyzed for genetic polymorphisms. The influence of genotype on pharmacokinetics and metabolism will be investigated by appropriate statistical methods, including population pharmacokinetic analyses. Genes to study would include MDR1 and SLC22A16, both involved in the transport of doxorubicin and AKR1A1 and CBR1, both involved in the reduction of doxorubicin to doxorubicinol. Selected genotypes will be incorporated as covariates into the population pharmacokinetic models developed. The potential impact of genetic variation will be evaluated in the context of other sources of variability such as age, weight, gender etc

Pharmacokinetic Study of Doxorubicin in Children With Cancer

Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia

Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.

Obtain one whole blood sample per patient, if separate consent was given.

Measure troponin T, troponin I, BNP, NT-proBNP, NT-proANP. Collect samples at two different doxorubicin infusions before and up to 1month after doxorubicin administration.

University Hospital Muenster

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
B-type Natriuretic Peptide in the Diagnosis of Heart Failure Related Ascites	NCT01150916	Heart Failure Liver Cirrhosis Ascites Carcinomatosis	BNP, SAAG, asci...	18 Years -	University of Sao Paulo
Pharmacokinetic Study of Doxorubicin in Children With Cancer	NCT01095926	Wilms Tumor Neuroblastoma Soft Tissue Sar... Acute Lymphobla...	doxorubicin	- 17 Years	University Hospital Muenster
B-type Natriuretic Peptide in the Diagnosis of Heart Failure Related Ascites	NCT01150916	Heart Failure Liver Cirrhosis Ascites Carcinomatosis	BNP, SAAG, asci...	18 Years -	University of Sao Paulo

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