Bacterial Infection, Benign Neoplasm, Malignant Neoplasm, Methicillin-Resistant Staphylococcus Aureus Infection, Myeloid Neoplasm, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia
Conditions
Brief summary
This randomized phase III trial studies chlorhexidine gluconate cleansing to see how well it works compared to control cleansing in preventing central line associated bloodstream infection and acquisition of multi-drug resistant organisms in younger patients with cancer or undergoing donor stem cell transplant. Chlorhexidine gluconate may help reduce bloodstream infections and bacterial infections associated with the central line.
Detailed description
PRIMARY OBJECTIVES: I. To determine whether chlorhexidine gluconate (CHG) cleansing decreases central line associated bloodstream infection (CLABSI) in children with cancer or those receiving an allogeneic hematopoietic cell transplantation (HCT). SECONDARY OBJECTIVES: I. To determine whether CHG cleansing decreases acquisition of multi-drug resistant organisms (MDRO: vancomycin resistant enterococci \[VRE\], methicillin resistant Staphylococcus aureus \[MRSA\], etc.) in children with cancer or those receiving allogeneic HCT. II. To determine whether CHG cleansing in children with cancer or those receiving allogeneic HCT is associated with cutaneous bacterial isolates with reduced susceptibility to CHG. III. To determine whether CHG cleansing decreases positive blood cultures in children with cancer or those receiving allogeneic HCT. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive CHG cleansing with topical skin wipes once daily (QD) for 90 days. ARM II: Patients receive control cleansing with topical skin wipes QD for 90 days.
Interventions
PROCEDUREChlorhexidine Gluconate Skin Cleanser
Given CHG cleansing
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDUREMild Soap Skin Cleanser
Given control cleansing
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Months to 21 Years
Healthy volunteers
No
Inclusion criteria
* TRANSPLANT PATIENTS: all patients undergoing planned allogeneic transplant (both malignant and non-malignant diagnoses) * ONCOLOGY PATIENTS: patients with an oncology diagnosis that are or will be on a chemotherapy regimen that will last for an additional \>= 3 months or are on or will be on a chemotherapy regimen for \< 3 months and then proceed to transplant (allogeneic or autologous stem cell rescue) during the 3-month study period * Patients undergoing allogeneic transplant must have, or be scheduled to have, an external tunneled central venous catheter (CVC) (Broviacs, Hickmans, tunneled percutaneously inserted central catheter \[PICCs\], etc.) and/or non-tunneled percutaneously inserted central catheter (PICC) that is expected to remain in place for an additional \>= 3 months * Patients with acute myelogenous leukemia (AML) or relapsed acute lymphoblastic leukemia (ALL) that will receive chemotherapy with/without transplant must have, or be scheduled to have, an external tunneled CVC (Broviacs, Hickmans, tunneled PICCs, etc.) and/or non-tunneled PICC that is expected to remain in place for an additional \>= 3 months * All other oncology patients that will receive chemotherapy with/without transplant must have, or be scheduled to have, an external tunneled CVC (Broviacs, Hickmans, tunneled PICCs, etc.) that is expected to remain in place for an additional \>= 3 months * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion criteria
* Patients with a previous or current line infection are ineligible until 14 days after the completion of antibiotics * Patients with only totally implanted CVCs or ports are ineligible * Patients with a known allergy or hypersensitivity to CHG are ineligible * Patients with chronic, severe, generalized skin breakdown (such as generalized blistering, burns, severe graft versus host disease \[GVHD\] with open sores, etc.) are ineligible * Patients currently enrolled on Children's Oncology Group (COG) study ACCL0934 are not eligible until they have completed the infection observation period of that study * Patients scheduled to receive broad-spectrum prophylactic antibacterial therapy are ineligible; patients only receiving prophylaxis for Pneumocystis pneumonia (PCP) (trimethoprim \[TMP\]/sulfamethoxazole \[SMX\]) or encapsulated organisms (penicillin) are eligible * Patients receiving sorafenib at the time of enrollment and those who are scheduled to receive sorafenib as part of a treatment plan are ineligible * Patients using prophylactic antimicrobial locks in the CVC at the time of enrollment and those who are scheduled to receive antimicrobial locks in the CVC as part of a treatment plan are ineligible * Patients previously enrolled on this trial are ineligible * Females who are pregnant or breastfeeding are ineligible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Central Line-associated Bloodstream Infections (CLABSI) Events During the At-risk Days | Up to 90 days post enrollment date | Rate of CLABSI per 1000 at-risk days. CLABSI outcome is defined according to the January 2015 Centers for Disease Control and Prevention (CDC) criteria. At risk days are defined as days with eligible central lines in place. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Multi-drug Resistant Organisms (MDRO) | Up to 90 days post enrollment date | MDROs are defined as Staphylococcus aureus resistant to oxacillin, Enterococcus spp. resistant to vancomycin, Klebsiella pneumoniae or Escherichia coli non-susceptible (intermediate or resistant) to ceftriaxone, ceftazidime, cefepime or any carbapenem, and Pseudomonas aeruginosa or Acinetobacter baumannii resistant to any carbapenem or ceftazidime, and either an aminoglycoside or fluoroquinolone. Clostridium difficile infection (CDI) is included as an MDRO and is defined as a positive lab test for C. difficile and \> 3 unformed stools in \< 24 hours. |
| Percentage of Patients Who Acquire Cutaneous Bacterial Isolates With Reduced Susceptibility to Chlorhexidine Gluconate (CHG) | Up to 90 days post enrollment date | Susceptibility to CHG is defined by MIC cutoff that is cutaneous staphylococcal isolate isolated from a follow-up swab with CHG MIC \> 4 ug/mL in patient without a resistant staphylococcal isolate isolated from a baseline swab. |
| Rate of Bacteremia Per 1000 At-risk Days | Up to 90 days post enrollment date | A bacteremia episode is defined any positive blood culture. At risk days are defined as days with eligible central lines in place. |
Countries
Canada, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (CHG Cleansing Wipe) Patients receive CHG cleansing with topical skin wipes QD for 90 days.
Chlorhexidine Gluconate Skin Cleanser: Given CHG cleansing
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies | 88 |
| Arm II (Control) Patients receive control cleansing with topical skin wipes QD for 90 days.
Laboratory Biomarker Analysis: Correlative studies
Mild Soap Skin Cleanser: Given control cleansing
Questionnaire Administration: Ancillary studies | 89 |
| Total | 177 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 5 |
| Overall Study | Ineligible | 0 | 2 |
| Overall Study | Physician Decision | 9 | 12 |
| Overall Study | Received Sorafenib after enrollment | 0 | 1 |
| Overall Study | Withdrawal by Subject | 31 | 15 |
Baseline characteristics
| Characteristic | Arm I (CHG Cleansing Wipe) | Arm II (Control) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 83 Participants | 88 Participants | 171 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 1 Participants | 6 Participants |
| Age, Continuous | 7.4 years STANDARD_DEVIATION 5.8 | 5 years STANDARD_DEVIATION 4.8 | 6.2 years STANDARD_DEVIATION 5.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 20 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants | 63 Participants | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 9 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 21 Participants | 36 Participants |
| Race (NIH/OMB) White | 51 Participants | 54 Participants | 105 Participants |
| Region of Enrollment Canada | 11 participants | 7 participants | 18 participants |
| Region of Enrollment United States | 77 participants | 82 participants | 159 participants |
| Sex: Female, Male Female | 35 Participants | 36 Participants | 71 Participants |
| Sex: Female, Male Male | 53 Participants | 53 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 88 | 3 / 86 |
| other Total, other adverse events | 22 / 88 | 14 / 86 |
| serious Total, serious adverse events | 0 / 88 | 2 / 86 |
Outcome results
Primary
Central Line-associated Bloodstream Infections (CLABSI) Events During the At-risk Days
Rate of CLABSI per 1000 at-risk days. CLABSI outcome is defined according to the January 2015 Centers for Disease Control and Prevention (CDC) criteria. At risk days are defined as days with eligible central lines in place.
Time frame: Up to 90 days post enrollment date
Population: 3 patients were excluded (2 ineligible and 1 withdrew consent) leaving 174 patients in the analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (CHG Cleansing Wipe) | Central Line-associated Bloodstream Infections (CLABSI) Events During the At-risk Days | 5.44 CLABSI per 1000 at-risk days. |
| Arm II (Control) | Central Line-associated Bloodstream Infections (CLABSI) Events During the At-risk Days | 3.1 CLABSI per 1000 at-risk days. |
Secondary
Percentage of Patients Who Acquire Cutaneous Bacterial Isolates With Reduced Susceptibility to Chlorhexidine Gluconate (CHG)
Susceptibility to CHG is defined by MIC cutoff that is cutaneous staphylococcal isolate isolated from a follow-up swab with CHG MIC \> 4 ug/mL in patient without a resistant staphylococcal isolate isolated from a baseline swab.
Time frame: Up to 90 days post enrollment date
Population: 135 participants contributed a baseline and at least one follow-up swab and were included in this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (CHG Cleansing Wipe) | Percentage of Patients Who Acquire Cutaneous Bacterial Isolates With Reduced Susceptibility to Chlorhexidine Gluconate (CHG) | 17.7 percentage of patients |
| Arm II (Control) | Percentage of Patients Who Acquire Cutaneous Bacterial Isolates With Reduced Susceptibility to Chlorhexidine Gluconate (CHG) | 5.5 percentage of patients |
Secondary
Percentage of Patients With Multi-drug Resistant Organisms (MDRO)
MDROs are defined as Staphylococcus aureus resistant to oxacillin, Enterococcus spp. resistant to vancomycin, Klebsiella pneumoniae or Escherichia coli non-susceptible (intermediate or resistant) to ceftriaxone, ceftazidime, cefepime or any carbapenem, and Pseudomonas aeruginosa or Acinetobacter baumannii resistant to any carbapenem or ceftazidime, and either an aminoglycoside or fluoroquinolone. Clostridium difficile infection (CDI) is included as an MDRO and is defined as a positive lab test for C. difficile and \> 3 unformed stools in \< 24 hours.
Time frame: Up to 90 days post enrollment date
Population: 3 patients were excluded (2 ineligible and 1 withdrew consent) leaving 174 patients in the analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (CHG Cleansing Wipe) | Percentage of Patients With Multi-drug Resistant Organisms (MDRO) | 15 Percentage of patients |
| Arm II (Control) | Percentage of Patients With Multi-drug Resistant Organisms (MDRO) | 12 Percentage of patients |
Secondary
Rate of Bacteremia Per 1000 At-risk Days
A bacteremia episode is defined any positive blood culture. At risk days are defined as days with eligible central lines in place.
Time frame: Up to 90 days post enrollment date
Population: 3 patients were excluded (2 ineligible and 1 withdrew consent) leaving 174 patients in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (CHG Cleansing Wipe) | Rate of Bacteremia Per 1000 At-risk Days | 7.24 bacteremia per 1000 at-risk days |
| Arm II (Control) | Rate of Bacteremia Per 1000 At-risk Days | 4.93 bacteremia per 1000 at-risk days |