Clinical trial NCT05133310: Effect of Simvastatin on Sepsis and Febrile Neutropenia in Patients With Acute Lymphoblastic Leukemia
Official title: Effect of Simvastatin on Sepsis and Febrile Neutropenia in Patients With Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Strains
Acute Lymphoblastic Leukemia
Sepsis
Keywords: Acute lymphoblastic leukemia
Sepsis
Febrile Neutropenia
Simvastatin
Lead sponsor: Hospital General de Mexico
Sponsor class: OTHER_GOV
First posted: 2021-11-24
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Clinical randomized trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Pregnant patients
* 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)

Primary outcomes:
measure: Hospital Discharge
timeFrame: 3 months
measure: Feverish Event
timeFrame: 3 months
measure: Sepsis
timeFrame: 3 months
measure: Neutrophils count
timeFrame: 3 months
measure: Platelets count
timeFrame: 3 month
measure: Blasts in marrow
timeFrame: 3 month
measure: Neutrophil recovery time
timeFrame: 1 month
Secondary outcomes:
measure: Bacterial isolation
timeFrame: 3 months
measure: Procalcitonin
timeFrame: 3 months
measure: Hospital Stay
timeFrame: 1 month
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Hospital General de México "Dr. Eduardo Liceaga"
Study officials:
affiliation: Hospital General de Mexico
name: Adolfo Martinez Tovar, PhD
role: STUDY_DIRECTOR
References:
citation: 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(Suppl 2):55-58.
citation: 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.
citation: 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.