Safety and Effectiveness of Novel Nitroglycerin Based Catheter Lock Solution

Study Overview
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Brief Summary
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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.

Official Title
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Phase 1/2 Study to Evaluate the Safety and Effectiveness of Novel Non-Antibiotic, Non-Heparin Nitroglycerin Based Catheter Lock Solution Used for the Prevention of Intraluminal Central Venous Catheter (CVC) Infections in Cancer Patients

Conditions
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Catheter-Associated Infections, Catheter-Related Infections

Intervention / Treatment
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* Drug: Nitroglycerin-citrate-ethanol (NiCE)


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitroglycerin-Citrate-Ethanol (NiCE)<br>Antimicrobial Nitroglycerin-Citrate-Ethanol catheter lock solution was administered for 2 hours then flushed | Drug: Nitroglycerin-citrate-ethanol (NiCE)<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From date of randomization until date of first Drug-Related Hypotension within 10 minutes of each flush, assessed up to 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 60 Days |