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| [ Print-friendly version ] |
| BENznidazole Evaluation For Interrupting Trypanosomiasis pilot trial |
| ISRCTN | ISRCTN13967269 |
| ClinicalTrials.gov identifier | |
| Public title | BENznidazole Evaluation For Interrupting Trypanosomiasis pilot trial |
| Scientific title | |
| Acronym | BENEFIT Pilot |
| Serial number at source | MCT-79704 |
| Study hypothesis |
Benznidazole is effective in producing parasitic cure in patients with Chronic Chagas Cardiomyopathy. 60 days of therapy with Benznidazole will:
1. Increase negativization of Trypanosomiasis cruzi as detected by Polymerase Chain Reaction (PCR) by at least 30%, and 2. Reduce t. cruzi parasite load by at least 50% |
| Ethics approval |
Approval received from the:
1. Research Ethics Board of Hamilton Health Sciences Corporation & McMaster University(Canada) on the 21st September 2006 (ref: NREC # 05-348) 2. Comité de Ethica em Pesquisa de l'Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (Brazil) on the 4th February 2004 (ref: NREC# 213/2004) 3. Ministerio de Salud y Ambiente (Argentina) on the 11th March 2005 (ref: NREC 1-0047-0000-00733-05-1) 4. Comite Investigaciones de Fundacion ABBOD SHAIO (Columbia) on 19th April 2004 |
| Study design | Multicentre, multinational, two arm, randomised parallel, controlled, placebo trial with study participant, study investigator, caregiver, outcome assessor, and data analyst blinding. |
| Countries of recruitment | Argentina, Brazil, Canada, Colombia |
| Disease/condition/study domain | Chagas disease; American trypanosomiasis |
| Participants - inclusion criteria |
1. Either sex, aged greater than or equal to 18 and less than or equal to 70 years
2. At least two positive serological tests for Chagas disease (indirect immunofluorescence, indirect hemagglutination, OR Enzyme-Linked Immunosorbent Assay [ELISA]) and at least ONE of the following markers of cardiac involvement (which identify individuals at high risk of progression): 2.1. Abnormal 12 lead Electrocardiogram (ECG): One-major criteria (second or third degree AV block) OR at least two minor criteria: 2.1.1. Any bundle branch block 2.1.2. Any fascicular block 2.1.3. Ventricular premature beats (greater than one) 2.1.4. First degree AV block greater than 220 ms, in the absence of drugs that slow AV node conduction 2.1.5. Mobitz type I AV block, in the absence of drugs that slow AV 2.1.6. Sinus bradycardia less than 50 bpm or sinus pauses greater than 3.0s, in the absence of sinus node blocking drugs 2.1.7. Low voltage of QRS in the frontal plane 2.1.8. Atrial fibrillation 2.2. Increased cardiothoracic ratio greater than 0.50 at baseline on upright chest X ray 2.3. Evidence of regional wall motion abnormality (hypokinesis, akinesis or dyskinesis) or reduced global Left Ventricular Systolic Function (LVEF) less than 50% (2D-Echo Radionuclide Angiography [RNA] LV ventriculography) or increased left ventricular diastolic diameter (greater than 55 mm) on 2D-Echo 2.4. Complex ventricular arrhythmias (multiform greater than 10/hour, couplets or non-sustained Ventricular Tachycardia [NSVT]) on 24 hour ambulatory ECG monitoring |
| Participants - exclusion criteria |
1. New York Heart Association (NYHA) heart failure class IV or decompensated heart failure
2. Evidence of concomitant Coronary Artery Disease (CAD) or other etiology of dilated cardiomyopathy 3. Previous treatment with antitrypanosomal agents or an accepted indication for antiparasitic therapy (e.g. reactivation of Chagas infection due to immunosuppression by several diseases or treatment with steroids) 4. Patients living in inadequate housing conditions that may predispose to t. cruzi re-infection will not be excluded; instead this condition will be appropriately documented 5. Inability to comply with follow-up 6. History of severe alcohol abuse within two years 7. Known chronic renal insufficiency (serum creatinine greater than 2.5 mg/dl or 200 umol) or hepatic insufficiency (Aspartate Aminotransferase [AST]/Alanine Aminotransferase [ALT] greater than 3 x normal) 8. Pregnancy or breast feeding 9. Megaesophagus with swallowing impairment 10. Other severe disease significantly curtailing life expectancy |
| Anticipated start date | 01/03/2006 |
| Anticipated end date | 30/04/2009 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 600 |
| Interventions |
1. Benznidazole: 60 days of treatment at 5 mg/kg/day given twice a day (at maximum dose of 400 mg/day)
2. Matching placebo: 60 days of treatment at 5 mg/kg/day given twice a day (at maximum dose of 400 mg/day) |
| Primary outcome measure(s) |
There are two related co-primary outcomes:
1. Negativisation and reduction of t. cruzi detected by PCR at the end of treatment which lasted 60 days, and at a two-year follow-up 2. Reduction in the mean burden of t. cruzi (parasite load) as detected by the concentration of t. cruzi/ml of blood by PCR in the treated group, at the end of treatment which lasted 60 days, and at a two-year follow-up |
| Secondary outcome measure(s) |
1. Safety and tolerability of benznidazole in chronic Chagas cardiomyopathy, 11 ± 2 days after initial randomisation, three weeks ± 3 days after randomisation, end of therapy (60 days) and two years later
2. Long-term feasibility of conducting a Randomised Controlled Trial (RCT) in patients with Chagas disease measured by patient enrolment and completion of follow-up, recruitment rate measured at baseline, completion measured at the end of therapy (60 days later), and two years later 3. Cardiovascular events: 3.1. Composite of major cardiovascular outcomes defined as the first occurrence of: death, cardiac arrest, sustained ventricular tachycardia, symptomatic heart failure, pacemaker or implantable cardiac defibrillator insertion, ischemic stroke or other systemic thromboembolic event, 11 days, 21 days, 60 days, 6 months, 1 year and 2 year after randomisation 3.2. New development of any of the following echo changes: segmental wall motion abnormalities, ventricular aneurysm, reduction in LV ejection fraction greater than 5%, increase in Left Ventricular end-Diastolic Dimension [LVDD] greater than 5.0 mm compared with baseline, 11 days, 21 days, 60 days, 6 months, 1 year and 2 year after randomisation 3.3. New 12 lead ECG alterations (complete bundle branch block, fascicular block, advanced atrio-ventricular block, atrial fibrillation, etc); 1st Degree AV Block PR greater than 280 ms, 11 days, 21 days, 60 days, 6 months, 1 year and 2 year after randomisation 3.4. Progression of NYHA functional class by at least one category, 11 days, 21 days, 60 days, 6 months, 1 year and 2 year after randomisation |
| Sources of funding | The Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-79704) |
| Trial website | |
| Publications | Protocol in http://www.ncbi.nlm.nih.gov/pubmed/18585495 |
| Contact name | Dr Carlos A Morillo |
| Address |
McMaster University
Population Health Research Institute HGH-McMaster Clinic 5th Floor, Room 501 237 Barton Street East Hamilton |
| City/town | Ontario |
| Zip/Postcode | L8L 2X2 |
| Country | Canada |
| Sponsor | Hamilton Health Science Corporation (HHSC) (Canada) |
| Address |
c/o Beena Cracknell
Population Health Research Institute CEBA McMaster University 1200 Main Street West Hamilton |
| City/town | Ontario |
| Zip/Postcode | L8N 3Z5 |
| Country | Canada |
| Tel | +1 905 527 4322 ext. 44555 |
| Fax | +1 905 570 0742 (RESEARCH) |
| beena@cardio.on.ca | |
| Sponsor website: | http://www.hamiltonhealthsciences.ca/ |
| Date applied | 01/06/2007 |
| Last edited | 04/08/2008 |
| Date ISRCTN assigned | 01/06/2007 |
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| © 2010 ISRCTN unless otherwise stated. | |
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