Efficacy and Safety of CUSA-081 in the Restoration of Central Venous Access Device (CVAD) Functionality

Phase 3TerminatedNCT03594175

Chiesi Farmaceutici S.p.A.462 enrolled

Overview

To evaluate the efficacy and safety of CUSA-081 (diluted reteplase) in the restoration of central venous access device (CVAD) functionality in participants 18 years and older.

This was a phase III, multinational, multicenter, randomized, double-blind, parallel-group, active and placebo-controlled study to examine CUSA-081 (diluted reteplase) versus placebo or alteplase in subjects with dysfunctional non-hemodialysis Central Venous Access Devices (CVADs). During the study, the treatment period consisted of 1 visit that may have taken place on the same day as screening or on the following day. After complying with all inclusion criteria, subjects were randomized in a 9:1:6 ratio to CUSA-081 : placebo : alteplase treatment group. A follow-up assessment was performed on Day 30 (±2 days) after treatment with study drug. The end of the study was defined as the last follow-up contact of the last subject to receive study drug in the study. Routine blood pressure measurement, heart rate and urine pregnancy test were performed before enrolment in the study. Throughout the study, safety assessment included evaluation of treatment emergent adverse events (TEAEs), adverse drug reactions (ADRs), and adverse events (AE) of Special Interest (AESI). CUSA-081 (reteplase) is a recombinant tissue plasminogen activator (tPA), currently approved in the USA (trade name: RETAVASE®) for treatment of acute ST-elevation myocardial infarction (STEMI) to reduce the risk of death and heart failure. Alteplase, a biosynthetic form of human tPA, Food and Drug Administration (FDA)-approved under the brand name ACTIVASE® for the treatment of acute ischemic stroke, acute myocardial infarction (AMI) to reduce mortality and incidence of heart failure, and acute massive pulmonary embolism for lysis.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

462

Conditions

Catheter Occlusion Thrombosis

Interventions

CUSA-081DRUG

Participants received 1 or 2 doses of CUSA-081 0.7 mg/2 mL directly into the catheter lumen

PlaceboDRUG

Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen

AlteplaseDRUG

Participants received 1 or 2 doses of alteplase, 2 mg/2 mL, directly into the catheter lumen

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 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 \> 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 instil 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. Exclusion Criteria: 1. CVAD (any type) used for hemodialysis; 2. CVAD known to be dysfunctional for more than 48 hours; 3. 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; 4. Known or suspected catheter related bloodstream infection (CRBSI); 5. 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 low molecular weight heparin (LMWH) for prophylaxis of thromboembolic events is allowed; 6. 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); 7. Uncontrolled hypertension (systolic BP ≥160 or diastolic BP ≥110 mmHg) at screening; 8. Clinically unstable in the opinion of the site investigator; 9. Known to be pregnant or breastfeeding at screening; 10. Previously treated in this study (READY 1) or in study READY 2; 11. History of allergic reaction to reteplase, alteplase or vial ingredients (excipients or diluents); 12. Use of any investigational drug or experimental medical device within 28 days prior to treatment; non interventional observational studies participation is allowed. 13. Not mentally, socially, or otherwise able to complete the trial assessment or not likely to survive beyond 30 days.

Locations (77)

Outcomes

Primary Outcomes

Percentage Of Participants With Treatment Success Following A Single Instillation Of Study Drug With A Dwell Time Up To 90 Min -- CUSA-081 vs Placebo -- Full Analysis Set (FAS)

CUSA-081 vs Placebo -- Single instillation of study drug -- Dwell Time Up To 90 Min -- Full Analysis Set (FAS) Treatment success was defined as the restoration of CVAD functionality, measured as the ability to withdraw 3 mL of blood and infuse 5 mL of saline. For this assessment, dwell time was up to 90 mins, after a single instillation of study drug. The percentage was calculated as the number of participants with treatment success divided by the total number of participants in the group, multiplied by 100%.

Time frame: Day 1 (up to 90 mins post dose)

Secondary Outcomes

Percentage Of Participants With Treatment Success Following A Single Instillation Of Study Drug With A Dwell Time Up To 90 Min -- CUSA-081 vs Alteplase -- Per Protocol Set (PP)

CUSA-081 vs Alteplase -- Single instillation of study drug -- Dwell Time Up To 90 Min -- Per Protocol set (PP) Treatment success was defined as the restoration of CVAD functionality, measured as the ability to withdraw 3 mL of blood and infuse 5 mL of saline. For this assessment, dwell time was up to 90 mins, after a single instillation of study drug. The percentage was calculated as the number of participants with treatment success divided by the total number of participants in the group, multiplied by 100%. The PP set was used for sensitivity analysis when testing for non-inferiority.

Time frame: Day 1 (up to 90 min post dose)

Percentage Of Participants With Treatment Success Following A Single Instillation Of Study Drug With A Dwell Time Up To 60 Min -- CUSA-081 vs Placebo -- Full Analysis Set (FAS)

CUSA-081 vs Placebo -- Single instillation of study drug -- Dwell Time Up To 60 Min -- Full Analysis set (FAS) Treatment success was defined as the restoration of CVAD functionality, measured as the ability to withdraw 3 mL of blood and infuse 5 mL of saline. For this assessment, dwell time was up to 60 mins, after a single instillation of study drug. The percentage was calculated as the number of participants with treatment success divided by the total number of participants in the group, multiplied by 100%.

Data from ClinicalTrials.gov

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