Catheter-Associated Infections, Catheter-Related Infections
Conditions
Brief summary
The objective of this Phase I/II pilot study is to evaluate the safety and effectiveness of a non- antibiotic chelator based lock solution that contains nitroglycerin in combination with sodium citrate and ethanol (NiCE lock solution) for prevention of central line associated bloodstream infection (CLABSI). * The primary objective of this study is to evaluate the safety and estimate the rate of adverse events associated with the NiCE lock solution. * The second primary objective is to estimate the rate of CLABSI in patients receiving the NiCE lock solution.
Interventions
DRUGNitroglycerin-citrate-ethanol (NiCE)
Lock solution instilled in catheter lumens for 2 hours then flushed. Administration for up to 30 days, daily as in-patient or once weekly as out-patient
Sponsors
M.D. Anderson Cancer Center
Novel Anti-Infective Technologies, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Inpatients who have a long term central venous catheter (CVC)-and the CVC has been in place for at least 14 days and is expected to remain in place at least for 30 days after enrollment * The CVC consists of a 5.0 French size, dual-lumen, peripherally inserted central catheter * Patients who are willing and capable to provide Informed Consent * Patients who are willing and capable to follow the instructions required to complete the study * Females (of child bearing potential) and males (of child bearing potential) must be abstinent or agree to use birth control during the study.
Exclusion criteria
* Patients who have an antimicrobial CVC. * Patients who have a short term CVC that have been placed in ICU (mainly rigid wall CVCs placed for acute care in ICU). * Patients who are hypotensive with a systolic blood pressure reading of \<110 mmHg at any time over the 3 days prior to study entry * Patients who are not awake, not alert, or who cannot express pain or discomfort related to the catheter locks * Patients with an existing local or systemic infection as defined by evidence of fever (a body temperature \> 38.0o C with two readings taken at least 10 minutes apart or one body temperature \> 38.3o) and any of the following within 24 hours of enrollment: Pulse rate \> 100 beats/min.; Respiratory rate \> 20/min.; WBC count \>12,000/mm3, \<4,000/mm3 or differential count showing \>10% band forms. Patient will still be eligible for the study if the participant's white blood cell count (WBC) is outside normal limits due to chemotherapy treatment or underlying conditions. Systolic blood pressure \<90 mm Hg. * Signs and symptoms of localized catheter-related infection (tenderness and/or pain, erythema, swelling, purulent exudates within 2 cm of entry site) * Patients with an occluded (partially or totally) catheter defined as inability to either withdraw blood or instill 3cc of fluid without resistance through any catheter lumen * Patients with multiple co-existing central venous catheters at the time of enrollment will not be enrolled. * Patients in whom the lock solution application will interfere with routine treatment of the underlying disease * Patients with a known history of allergic reaction to ethanol, nitroglycerin, or citrate. * Female patients who are pregnant or breast feeding * Patients who are on disulfiram, metronidazole or are dependent on alcohol * Patients receiving phosphodiesterase type 5 (PDE-5) inhibitors (such as sildenafil, tadalafil, vardenafil).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug-Related Hypotension | From date of randomization until date of first Drug-Related Hypotension within 10 minutes of each flush, assessed up to 60 days | Drug-related hypotension is defined as a significant drop in measured blood pressure (BP) that exceeds the normal BP variability of a patient by 30%, that is associated with clinical signs and symptoms (dizziness and syncope) and is unexplained by factors other than the lock solution (such as other antihypertensive drugs, sepsis, bleeding). BP variability will be based on the standard deviation (SD) of a patient's blood pressure measured in the 3 days preceding participation in this trial and will be calculated at the time of trial entry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Catheter-Associated Infections | 60 Days | Catheter-Associated Infections will be measured by microbiological culture defined as either Catheter-Related Bloodstream Infection (CRBSI) as defined by the Infectious Diseases Society of America (IDSA), particularly in neutropenic patients, or Central Line-Associated Bloodstream Infection (CLABSI) as defined by the Centers for Disease Control and Prevention (CDC), particularly in non-neutropenic patients |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NiCE Lock | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | NiCE Lock |
|---|---|
| Age, Continuous | 67 years |
| Median Standard Deviation of Systolic Blood Pressure | 7.86 mm Hg |
| Number of patients with Hypertension | 36 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Region of Enrollment United States | 60 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 38 Participants |
| Type of Cancer Acute Lymphatic Leukemia | 12 Participants |
| Type of Cancer Acute Monocytic Leukemia | 34 Participants |
| Type of Cancer Acute Myelogenous Leukemia | 2 Participants |
| Type of Cancer Aplastic Anemia | 1 Participants |
| Type of Cancer B cell Acute Lymphatic Leukemia | 1 Participants |
| Type of Cancer Biphenotypic acute leukemia | 1 Participants |
| Type of Cancer Chronic Lymphatic Leukemia | 1 Participants |
| Type of Cancer Chronic Monocytic Leukemia | 3 Participants |
| Type of Cancer Lymphoma | 1 Participants |
| Type of Cancer Myelodysplastic Syndrome | 3 Participants |
| Type of Cancer Myelofibrosis | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 60 |
| other Total, other adverse events | 2 / 60 |
| serious Total, serious adverse events | 0 / 60 |
Outcome results
Primary
Number of Participants With Drug-Related Hypotension
Drug-related hypotension is defined as a significant drop in measured blood pressure (BP) that exceeds the normal BP variability of a patient by 30%, that is associated with clinical signs and symptoms (dizziness and syncope) and is unexplained by factors other than the lock solution (such as other antihypertensive drugs, sepsis, bleeding). BP variability will be based on the standard deviation (SD) of a patient's blood pressure measured in the 3 days preceding participation in this trial and will be calculated at the time of trial entry.
Time frame: From date of randomization until date of first Drug-Related Hypotension within 10 minutes of each flush, assessed up to 60 days
Population: All patients receiving at least one dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NiCE Lock | Number of Participants With Drug-Related Hypotension | 0 Participants |
Secondary
Incidence of Catheter-Associated Infections
Catheter-Associated Infections will be measured by microbiological culture defined as either Catheter-Related Bloodstream Infection (CRBSI) as defined by the Infectious Diseases Society of America (IDSA), particularly in neutropenic patients, or Central Line-Associated Bloodstream Infection (CLABSI) as defined by the Centers for Disease Control and Prevention (CDC), particularly in non-neutropenic patients
Time frame: 60 Days
Population: 619 catheter days on NiCE Lock Solution / 1853 catheter days off NiCE Lock Solution
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NiCE Lock | Incidence of Catheter-Associated Infections | 0 infections per 1000 catheter days |
| Off NiCE Lock | Incidence of Catheter-Associated Infections | 1.6 infections per 1000 catheter days |