Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Ministry of Health, Brazil | OTHER_GOV |
Not provided
Not provided
Not provided
Neoplasia is the main cause of general death in the Brazilian population. In 2016, they were responsible for approximately 211,343 (16%) deaths, followed by cardiovascular diseases (12.6%). Despite the high mortality rate of neoplasia, oncological treatment have advanced substantially in recent decades improving the prognosis of patients. However, growing evidence suggest that some oncological agents may induce significant toxicity that may play a major role in the quality of life, morbidity and mortality. The cardiovascular system is often negatively affected with cancer therapy, predisposing several patients to stop appropriate treatments or to have cardiovascular events related to the cardiotoxicity. The most typical manifestation of cardiotoxicity and related consequences (heart failure) are related to the use of anthracyclines. Anthracyclines are part of the chemotherapy regimen for solid tumors and hematological neoplasms in children and adults, and are associated with an increase in life expectancy. Carvedilol is an α and β-blocker that also has antioxidant properties. Preliminary studies have shown that carvedilol and its metabolites prevent lipid peroxidation, inhibit the formation and inactivate free radicals, in addition to preventing the depletion of endogenous antioxidants, such as vitamin E. These effects would potentially prevent anthracycline injury but definitive evidence is still needed. This is a multi-center, double-blind, randomized, placebo-controlled study that aims to establish the efficacy of carvedilol for the primary prevention of left ventricular systolic dysfunction in cancer patients obtained with anthracycline chemotherapy, in different schedules and doses.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention Group | Experimental | Patients allocated to the intervention group will receive carvedilol 6.25 mg twice daily, then increased to 12.5 mg twice daily, until maximum dose of 25 mg twice daily according to the patients' tolerance; The dosis increments will occur every 5 days. If after the increment the patient develops bradycardia or hypotension, the dose will be reduced to the maximum tolerated dose. Carvedilol will ideally be maintained for up to 30 days after the end of chemotherapy. |
|
| Control Group | Placebo Comparator | Patients allocated to this group will receive placebo in a presumably staggered and progressive manner similar to the group intervention. The placebo will ideally be maintained for up to 30 days after the end of chemotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carvedilol | Drug | Carvedilol will be dispensed in a staggered and progressive manner, initially from 6.25 mg twice daily, then increased to 12.5 mg twice daily, until maximum dose of 25 mg twice daily or development of contraindications |
| Measure | Description | Time Frame |
|---|---|---|
| Drop in ejection fraction within 12 months of starting treatment. | Drop in ejection fraction> 10% to values less than 50% of the left ventricle | 12 months |
| Cardiac events within 12 months of starting treatment. | Cardiac events such as death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Drop in ejection fraction within 12 months. | Drop in ejection fraction greater than 10% and values less than 55% | 12 months |
| Reduction in myocardial strain in 12 months from the start of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Diagnosis of neoplasia within 12 months. | Diagnosis of another neoplasia | 12 months |
| Progression of oncological disease within 12 months. | Progression of oncological disease |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ana Cecilia A Silva, MD, PhD | Contact | +551133944094 | ana.ceasilva@hsl.org.br | |
| Isabela B dos Santos da Silva, MD, PhD | Contact | +551133944094 | isabela.bsscosta@hsl.org.br |
| Name | Affiliation | Role |
|---|---|---|
| Renato H D. lopes, MD, PhD | Hospital Sirio-Libanes | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Sirio Libanes | Recruiting | São Paulo | São Paulo | 01308-050 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39988204 | Derived | Costa IBSDS, Furtado RHM, Drager LF, de Barros E Silva PGM, Melo MDT, Araruna P, Bacchiega BC, Cauduro S, Walter E, Fialho GL, Silvestre O, Damiani LP, Barbosa LM, Luz MN, Silva ACA, de Mattos RR, Saretta R, Rehder MHHS, Hajjar LA, Lopes-Fernandez T, Dent S, Gibson CM, Lopes RD, Kalil Filho R; on behalf the CARDIOTOX Investigators. Effects of carvedilol on the prevention of cardiotoxicity induced by anthracyclines: Design and rationale of the CARDIOTOX trial. Am Heart J. 2025 Jul;285:1-11. doi: 10.1016/j.ahj.2025.02.014. Epub 2025 Feb 22. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D066126 | Cardiotoxicity |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077261 | Carvedilol |
| ID | Term |
|---|---|
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Randomization will be in the proportion of 1: 1 (carvedilol x placebo). Both randomization and allocation of patients will be chosen in a veiled manner to patients and to assess. Data on randomization and allocation will be under custody of the Data analysis and safety committee.
| Placebo | Drug | Patients will receive placebo in a presumed staggered and progressive manner similar to the intervention group. The placebo will ideally be maintained for up to 30 days after the end of chemotherapy. |
|
Relative reduction of more than 15% in myocardial strain
| 12 months |
| Diastolic dysfunction within 12 months | Development of diastolic dysfunction within 12 months | 12 months |
| Elevation of biomarkers during chemotherapy and up to 12 months of follow-up | Elevation of biomarkers (NT-pro BNP and troponin) during chemotherapy and up to 24 months of follow-up | 12 months |
| Quality of life (EuroQol-5D). | Quality of life measured by questionnaire in up to 12 months. | 12 months |
| Cardiovascular complications in 12 months. | Cardiovascular complications (death, resuscitated cardiac arrest, myocardial infarction, heart failure and cardiac arrhythmias) in 24 months. | 12 months |
| 12 months |
| Tumor recurrence within 12 months. | Tumor recurrence | 12 months. |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
| D020005 |
| Propanols |
| D000588 | Amines |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |