According to data from the U.S. CF Foundation Patient Registry (USCFFPR), more than 25% of children and 40% of adults were treated with intravenous (IV) antibiotics for pulmonary exacerbations (PEx) in 2016. This translated to 20,286 care episodes and nearly 300,000 catheter-days of risk exposure (1). Medication is typically administered through peripherally inserted central catheters (PICCs), midline catheters or totally implantable venous access devices (TIVADs) The decision to place a PICC or TIVAD in a given patient is largely a subjective one, dependent on patient and physician experiences and preferences. PICCs have become accepted as a part of usual care for pulmonary exacerbations and are generally considered safe and well-accepted by patients (2).

Case series have identified important complications of PICCs and TIVADs in patients such as deep venous thrombosis (DVT) and central line associated bloodstream infection (CLABSI) (3-10); central venous stenosis (11); and other types of mechanical dysfunction (12). In contrast to patients with other diseases who usually undergo PICC placement for a single treatment, however, CF patients often require repeated instrumentation over many years. This fundamental difference in how PICCs are employed confounds extrapolation of findings from studies in non-CF populations to CF patients. The incidence of PICC-associated DVT in CF patients ranges from 2 to 8% (9, 13). Catheter-related complications may delay completion of therapy and expose patients to repeated vascular access procedures and risks associated with systemic anticoagulation in cases of thrombosis. Furthermore, devastating complications, such as central venous stenosis (Figure 1), may discourage patients from subsequently accepting IV antibiotics. Therefore, it is critically important to identify patient- and device-related attributes associated with increased likelihood of complications and to devise strategies to mitigate these risks.

Proposed risk factors in CF patients fall into several broad categories. First are catheter-related factors: larger catheter size (13, 14), number of catheter lumens (13, 14), and catheter composition (10, 15). Second are patient factors: lung function (14), nutritional status (14, 16), respiratory flora (14, 17, 18), diabetes status (19-21), thrombophilia (22); and number of previously placed or guidewire-exchanged catheters (14, 23). Third are catheter-management factors: insertion technique and site selection (24-27), inpatient versus outpatient care (28), anticoagulant use (29), blood sampling practices (30), line flushing solutions (31), frequency of dressing changes (32), and duration of line use (33). The importance of many of these factors remains controversial, leading some to call for detailed prospective studies of PICC use in specific patient populations (34). To date, no multicenter trial has prospectively studied PICC and midline catheter-associated complications in adult and pediatric CF patients. We hypothesize that the rate of PICC and midline vascular complications among C Fpatients is associated with specific patient level and line level factors as well as with line insertion and management practices.

Specific Aims

Specific Aim #1: To confirm associations between patient level factors and risk of subsequent PICC and midline complications and evaluate the strength of any associations.

Specific Aim #2: To confirm associations between catheter level factors and risk of subsequent PICC and midline complications and evaluate the strength of any associations

Specific Aim #3: To confirm associations between catheter management factors and risk of subsequent PICC and midline complications and evaluate the strength of any associations

Primary Endpoint: The primary endpoint is the occurrence of vascular complications, defined as occlusion of the catheter requiring removal or symptomatic venous thrombosis in the extremity with the line as indicated by a Constans Clinical Decision Score > 2 during the time the catheter is in place (the definition does not require ultrasound confirmation, though this information will be collected, if an ultrasound is performed).

Secondary Endpoints: Bacteremia, fungemia, local phlebitis or superficial thrombophlebitis, hematoma, bleeding (including incident hemoptysis after use of thrombolytic agents), site pain, arm circumference at the level of catheter insertion, catheter fracture, temporary occlusion of the catheter cleared by thrombolytic agent, non-occlusive venous thrombosis as evidenced by ultrasound or DVT at another site, blood markers of inflammation and measures of coagulation status.

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