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

Phase 4

• Conditions: Acute Lymphoblastic Leukemia; Strains; Sepsis
• Interventions: Drug: Simvastatin

• Registration Number: NCT05133310
• Lead Sponsor: Hospital General de Mexico

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.

Study Timeline

• Study First Submitted: 2021-11-15
• Study First Submitted QC: 2021-11-15
• Study Start: 2021-11-19
• Study First Posted: 2021-11-24
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-02
• Last Update Posted: 2022-01-04
• Primary Completion: 2022-12-16
• Study Completion: 2023-06-23

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 108

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Simvastatin Treatment Group	Simvastatin	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.

Primary Outcome Measures

Name	Time	Method
Neutrophils count	3 months	Number of neutrophils found in peripheral blood at the end of each chemotherapy cycle
Feverish Event	3 months	Determination of a temperature above 38 ° persistently for more than 30 minutes
Hospital Discharge	3 months	The event in which patient is discharge from Hospital stay,
Sepsis	3 months	Presence of hemodynamic alterations characterized by persistent hypotension, elevated heart rate, fever, and abnormal respiration
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

Name	Time	Method
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

Trial Locations

Locations (1)

Hospital General de México "Dr. Eduardo Liceaga"; 🇲🇽 Mexico City, Mexico