Effect of Simvastatin on Sepsis and Febrile Neutropenia in Patients With Acute Lymphoblastic Leukemia
In general, the percentage of complete remissions is 85 - 90 % for acute lymphoid leukemia (ALL). In developing countries, percentages are lower secondary to higher sepsis-related mortality. Although the effect of statins on inflammatory response associated with sepsis has been demonstrated, including an effect on bacterial proliferation in patients with a state of immunosuppression, their effect has not been demonstrated so far in patients with hemato-oncological cancer.
|Condition or Disease
Death associated with sepsis is one of the principal complications related to chemotherapy treatment; there are currently no strategies to prevent its development besides the use of prophylactic antibiotics or granulocyte colony stimulants to reduce the period of febrile neutropenia. Most of the trials on the use of statins are retrospective with controversial results and include patients with different clinical situations that conditioned the septic study.
Arms and Interventions
|No Intervention: Standard Care Group
Patients will receive the standard chemotherapy regimen assigned for their treatment and, they will be followed and monitored until the end of treatment and hospitalization.
|Experimental: Simvastatin Treatment Group
Patients will combine the standard CALGB treatment scheme plus Simvastatin 10mg orally every 24 hours during the first 7 days of treatment and then continue with 20mg every 24 hours until the end of treatment and hospitalization.
Combination of Simvastatin with Standard Chemotherapy scheme for acute lymphoblastic patients.
Primary Outcome Measures
- Hospital Discharge [3 months]
The event in which patient is discharge from Hospital stay,
- Feverish Event [3 months]
Determination of a temperature above 38 ° persistently for more than 30 minutes
- Sepsis [3 months]
Presence of hemodynamic alterations characterized by persistent hypotension, elevated heart rate, fever, and abnormal respiration
- Neutrophils count [3 months]
Number of neutrophils found in peripheral blood at the end of each chemotherapy cycle
- Platelets count [3 month]
Number of platelets found in peripheral blood at the end of each chemotherapy cycle
- Blasts in marrow [3 month]
Presence of more than 5% of blasts in bone marrow after each chemotherapy cycle
- Neutrophil recovery time [1 month]
Time in days for neutrophil recovery
Secondary Outcome Measures
- Bacterial isolation [3 months]
Description of the germ isolated in cultures during follow-up
- Procalcitonin [3 months]
Biomarker used in infectious and inflammatory processes associated mainly with gram-negative germs, this measurement is routine in the follow-up of individuals with febrile neutropenia
- Hospital Stay [1 month]
Measurement of days of hospital stay
Patients diagnosed with acute leukemia under treatment of a chemotherapy regimen
Stable performance status (ECOG: 0 or Karnofsky scale greater than 80%) at time of analysis and under chemotherapy regimen
Life expectancy greater than 48 hours after diagnosis
Oral route available
Have signed informed consent at the time of the study
Patients whose chemotherapy regimen is administered in a hospital rather than an outpatient manner
Patients with acute leukemias over 55 years of age and with impaired functional status at the time of diagnosis
Elevation of liver enzymes 3 times higher than the range established by the central laboratory
Persistent kidney involvement despite having adequate hydration
Patients with peripheral neuropathy considered severe or disabling grade
Patients with a history of psychiatric disorders or psychotic attacks
Individuals who do not have the oral route available, who are maintained with a nasogastric tube, or who require support for the diagnosis through parenteral nutrition
Patients undergoing peritoneal dialysis or hemodialysis treatment
Patients with leukemia associated with Down syndrome
Patients under low-intensity chemotherapy regimen or palliative regimen
Previous allergy to any statin component
Patients with a history of liver failure (Child-Pugh Stage B or C)
Contacts and Locations
|Hospital General de México "Dr. Eduardo Liceaga"
Sponsors and Collaborators
- Hospital General de Mexico
- Study Director: Adolfo Martinez Tovar, PhD, Hospital General de Mexico
Study Documents (Full-Text)None provided.
- Escrihuela-Vidal F, Laporte J, Albasanz-Puig A, Gudiol C. Update on the management of febrile neutropenia in hematologic patients. Rev Esp Quimioter. 2019 Sep;32 Suppl 2:55-58. Review.
- Pertzov B, Eliakim-Raz N, Atamna H, Trestioreanu AZ, Yahav D, Leibovici L. Hydroxymethylglutaryl-CoA reductase inhibitors (statins) for the treatment of sepsis in adults - A systematic review and meta-analysis. Clin Microbiol Infect. 2019 Mar;25(3):280-289. doi: 10.1016/j.cmi.2018.11.003. Epub 2018 Nov 23.
- Pirzad Jahromi G, P Shabanzadeh A, Mokhtari Hashtjini M, Sadr SS, Rasouli Vani J, Raouf Sarshoori J, Charish J. Bone marrow-derived mesenchymal stem cell and simvastatin treatment leads to improved functional recovery and modified c-Fos expression levels in the brain following ischemic stroke. Iran J Basic Med Sci. 2018 Oct;21(10):1004-1012. doi: 10.22038/IJBMS.2018.29382.7100.