Effect of Simvastatin on Sepsis and Febrile Neutropenia in Patients With Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Simvastatin on Sepsis and Febrile Neutropenia in Patients With Acute Lymphoblastic Leukemia

Conditions
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Strains, Acute Lymphoblastic Leukemia, Sepsis

Intervention / Treatment
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* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Clinical randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Care Group<br>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<br>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. | Drug: Simvastatin<br>* Combination of Simvastatin with Standard Chemotherapy scheme for acute lymphoblastic patients.<br>* Other names: Intervention Group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Discharge | The event in which patient is discharge from Hospital stay, | 3 months | 
| Feverish Event | Determination of a temperature above 38 ° persistently for more than 30 minutes | 3 months | 
| Sepsis | Presence of hemodynamic alterations characterized by persistent hypotension, elevated heart rate, fever, and abnormal respiration | 3 months | 
| Neutrophils count | Number of neutrophils found in peripheral blood at the end of each chemotherapy cycle | 3 months | 
| Platelets count | Number of platelets found in peripheral blood at the end of each chemotherapy cycle | 3 month | 
| Blasts in marrow | Presence of more than 5% of blasts in bone marrow after each chemotherapy cycle | 3 month | 
| Neutrophil recovery time | Time in days for neutrophil recovery | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bacterial isolation | Description of the germ isolated in cultures during follow-up | 3 months | 
| Procalcitonin | 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 | 3 months | 
| Hospital Stay | Measurement of days of hospital stay | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute lymphoblastic leukemia, Sepsis, Febrile Neutropenia, Simvastatin