This is a phase III, multinational, multicenter, randomized, double-blind, parallel-group, active, and placebo-controlled study to examine CUSA-081 versus placebo or alteplase in subjects with dysfunctional non-hemodialysis Central Venous Access Devices (CVADs).
The treatment period will consist of one visit during the study, which may occur on the same day as screening or the following day. After meeting all inclusion criteria, subjects will be randomized in a 9:1:6 ratio of CUSA-081: placebo: alteplase.
A follow-up assessment will be performed on Day 30 (±2 days) after treatment with the study drug.
Routine blood pressure measurement, heart rate, and a urine pregnancy test will be performed before enrollment in the study.
Safety, including Treatment-Emergent AEs (TEAEs), Adverse Drug Reactions (ADRs), and Adverse Events of Special Interest (AESI), will be recorded throughout the study. The end of the trial is defined as the last follow-up contact of the last subject to receiving the study drug in the trial.
- 1. Inability to have 3 mL of blood withdrawn from the selected study catheter;
- 2. A single or multi-lumen CVAD, implanted ports or peripherally inserted central catheters (PICCs) in place for more than 24 hours and documented as previously being patent and functional;
- 3. Ability to designate one dysfunctional lumen of a multi-lumen catheter to be used throughout the study for both study drug instillation and assessment of CVAD function;
- 4. Male and non-pregnant female subjects from all racial and ethnic groups 18 years of age and older;
- 5. Able to have fluids infused at the volume necessary to instill study drug into the CVAD (i.e., up to 2 mL);
- 6. Informed consent form (ICF) signed and dated indicating that the subject has been informed of and agreed with all pertinent aspects of the study and is willing to comply with all study requirements and procedures.
12. Non-interventional observational studies participation is allowed. Not mentally, socially, or otherwise able to complete the trial assessment or not likely to survive beyond 30 days.
- 1. CVAD (any type) used for hemodialysis; CVAD known to be dysfunctional for more than 48 hours;
- 2. Reasonable evidence of mechanical or non-thrombotic occlusion in the selected study catheter (e.g., catheter malposition or migration, sutures, kinks, or precipitates causing obstruction), radiographic assessment is not required;
- 3. Known or suspected catheter-related bloodstream infection (CRBSI);
- 4. Use of any fibrinolytic agent or anticoagulant (e.g., alteplase, tenecteplase, reteplase, urokinase, or heparin) within 24 hours prior to the treatment period (first instillation of study drug). Use of subcutaneous LMWH for prophylaxis of thromboembolic events is allowed;
- 5. Known to be at high risk for bleeding events or embolic complications in the opinion of the Investigator, or has a known condition for which bleeding constitutes a significant hazard (e.g., recent stroke, recent intracranial or intraspinal surgery or serious head trauma, intracranial neoplasm, arteriovenous malformation or aneurysm, known bleeding diathesis);
- 6. Uncontrolled hypertension (systolic BP =160 or diastolic BP =110 mmHg) at screening;
- 7. Clinically unstable in the opinion of the site investigator;
- 8. Known to be pregnant or breastfeeding at screening;
- 9. Previously treated in this study (READY 1) or study READY 2;
- 10. History of allergic reaction to reteplase, alteplase, or vial ingredients (excipients or diluents);
- 11. Use of an investigational drug or experimental medical device within 28 days before treatment;