PR-0164 First in Human Clinical Trial of the PAVmed PortIO Intraosseous Infusion System

Study Overview
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Brief Summary
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The PortIO is intended to provide non-emergent vascular access in chronic kidney disease (CKD) patients where preservation of venous anatomy is desired and iatrogenic damage to the veins should be avoided and/or patients with poor/difficult vascular access. The PortIO device may be inserted into the proximal or distal tibia or the proximal humerus in adults, and provides up to 60 days of intraosseous vascular access for delivery of fluids and medications.

Detailed Description
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This is a prospective, open label, single arm, non-randomized, multicentric first in human clinical trial of the PortIO device for intraosseous infusion of fluids and/or medications for up to 60 days in subjects that meet the inclusion criteria. Both hospitalized patients as well as outpatients can be screened and, if appropriate, can be consented and enrolled into the study. They will have the PortIO device implanted by a qualified physician and then undergo prescribed infusions as needed and determined by the treating physician over either a 7-day or a 60-day period. The device will then be removed after the 7 days or 60 days of use and the subject followed up at 30 days after explant.

Official Title
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First in Human Clinical Trial of the PAVmed PortIO Intraosseous Infusion System to Evaluate Safety and Performance

Conditions
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Chronic Kidney Disease stage3, Chronic Kidney Disease stage4, Chronic Kidney Disease Stage 5, Poor Vascular Access

Intervention / Treatment
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* Device: PAVmed PortIO™ Intraosseous Infusion System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet the following criteria are eligible for participation in the study: Subject is > 22 years old Subject has grade 3 or higher CKD and is receiving or may receive renal replacement therapy with hemodialysis OR has poor/difficult vascular access. Subject does NOT need urgent or emergent vascular access; Subject, or authorized representative, signs a written Informed Consent form to participate in the study, prior to any study mandated procedures Subject is willing and able to complete follow-up requirement Exclusion Criteria: Subjects must be EXCLUDED from participation in this study if ANY of the following criteria are met: Fracture (within 6 months), bone tumor, or structural bone abnormality (such as osteogenesis imperfect, avascular necrosis, and severe osteoporosis) of the target bone Excessive overlying soft tissue, nerves, arteries, tendons or absence of anatomic landmarks at the target site Previous orthopedic procedure at or near the insertion site (e.g. artificial joint, rigid fixation hardware) IO access or attempted IO access in the target bone within 7 days Known or suspected allergy to any device component or materials contained in the device Local tissue factors preventing proper device stabilization and / or access including local infection, fragile tissue and absence of adequate or excessive overlying soft tissue. Subject with known unstable cardiac disease (recent MI within 30 days, cardiac surgery within 6 months, unstable angina, severe aortic stenosis/regurgitation, severe congestive heart failure, severe mitral stenosis/regurgitation), uncontrolled diabetes (blood glucose >240 mg/dl) or subjects on immunosuppressive medications (e.g. organ transplant patients) Subjects who are anticipated to receive infusion of blood or blood products, chemotherapeutic agents, hypertonic solutions, caustic agents or any agents known to harm bone marrow or cause bone marrow suppression such as azathioprine, procainamide, sulfasalazine via the test device. Insertion into the humerus on the same side as a previous mastectomy Known allergy to contrast media or local anesthetics (e.g. lidocaine, bupivacaine) Subjects with known bleeding disorders including thrombocytopenia, thrombasthenia, hemophilia or Von Willebrand's disease. Subjects with a history of hypercoagulable disorders such as protein S or C deficiency, Factor 5 Leiden resistance, Antithrombin III deficiency, Antiphospholipid antibody syndrome, Heparin Induced Thrombocytopenia etc. Subjects who are anticipated to need power injections via the test device for CT scan or angiography Subject has other medical, social or psychological problem that in the opinion of the investigator precludes them from fully participating Women who are pregnant, women who are attempting to become pregnant, as well as women who are breast feeding.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 99 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Total Sample Size<br>The total sample size will be up to 40 subjects that complete the full intended implant durations of either 7 days (n=up to 10) or60 days (n=up to 30). Group 1 patients will be enrolled first and at least 5 patients will complete the 7-day implant duration before Group 2 patients begin enrollment. Group 1 and Group 2 subjects can be screened in parallel. Group 2 enrollment will start immediately after at least 5 subjects in Group 1 have successfully completed the 7-day implantation period. Study subjects will have the PortIO device implanted by a qualified physician (Table 5) and then undergo prescribed, standard of care infusion regimen as determined by their treating physician over either the 7-day or the 60-day period. After the intended implant duration and use during the implant period, the device will then be removed and the subject will be followed for safety at 30 days after explant. | Device: PAVmed PortIO™ Intraosseous Infusion System<br>* The PortIO is intended to provide non-emergent vascular access in chronic kidney disease (CKD) patients where preservation of venous anatomy is desired and iatrogenic damage to the veins should be avoided and/or patients with poor/difficult vascular access. The PortIO device may be inserted into the proximal or distal tibia or the proximal humerus in adults, and provides up to 60 days of intraosseous vascular access for delivery of fluids and medications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Performance | Incidence of successful implant in the target anatomic location; Patency through the implant duration, with final patency assessment performed immediately prior to device explant; Incidence of successful device explant | Entire duration of Study an average of 2 years | 
| Primary Safety | Incidence of serious device-related adverse events | Entire duration of Study and average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint | Incidence of all device-related adverse events, whether serious or non-serious | Entire duration of Study an average of 2 years |