Clinical trial NCT03594175: Efficacy and Safety of CUSA-081 in the Restoration of Central Venous Access Device (CVAD) Functionality
Official title: A Phase 3, Randomized, Double-Blind, Active and Placebo-Controlled Study on the Use of CUSA-081 for Dysfunctional Central Venous Access Devices (CVADs)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Catheter Occlusion
Thrombosis
Keywords: Central Venous Access Device (CVAD)
CUSA-081
reteplase
alteplase
occluded catheters
catheter
occlusion
thrombosis
thrombotic occlusion
CVAD
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2018-07-20
Enrollment: 462
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Day 1 (up to 90 mins post dose)
Secondary outcomes:
measure: 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)
timeFrame: Day 1 (up to 90 min post dose)
measure: 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)
timeFrame: Day 1 (up to 60 min post dose)
measure: Percentage Of Participants With Treatment Success Following 2 Instillations Of Study Drug With A Dwell Time Up To 180 Min -- CUSA-081 vs Placebo -- Full Analysis Set (FAS)
timeFrame: Day 1 (up to 180 min post dose)
measure: 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 -- Full Analysis Set (FAS)
timeFrame: Day 1 (up to 90 min post dose)
measure: Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug
timeFrame: Day 1 (post dose) up to Day 30
measure: Percentage of Participants With Treatment-emergent Adverse Events (AEs) Leading to Study Discontinuation
timeFrame: Day 1 (start of treatment) and until the end of the treatment period (up to 180 min post dose).
measure: Percentage of Participants With Treatment-emergent Adverse Events (AEs) of Special Interest (AESI)
timeFrame: Day 1 (start of treatment) and until the end of the treatment period (up to 180 min post dose).
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Chiesi Investigational Site
state: Arkansas
city: Redlands
country: United States
facility: Chiesi Investigational Site
state: California
city: Stockton
country: United States
facility: Chiesi Investigational Site
state: California
city: Norwich
country: United States
facility: Chiesi Investigational Site
state: Connecticut
city: Newark
country: United States
facility: Chiesi Investigational Site
state: Delaware
city: Jacksonville
country: United States
facility: Chiesi Investigational Site
state: Florida
city: Miami
country: United States
facility: Chiesi Investigational Site
state: Florida
city: Plantation
country: United States
facility: Chiesi Investigational Site
state: Florida
city: Weeki Wachee
country: United States
facility: Chiesi Investigational Site
state: Florida
city: Weston
country: United States
facility: Chiesi Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Chiesi Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: Chiesi Investigational Site
state: Hawaii
city: Quincy
country: United States
facility: Chiesi Investigational Site
state: Illinois
city: New Albany
country: United States
facility: Chiesi Investigational Site
state: Indiana
city: Topeka
country: United States
facility: Einspahr
state: Kansas
city: Lewiston
country: United States
facility: Chiesi Investigational Site
state: Maine
city: Hannibal
country: United States
facility: Chiesi Investigational Site
state: Missouri
city: Kalispell
country: United States
facility: Chiesi Investigational Site
state: Montana
city: Omaha
country: United States
facility: Chiesi Investigational Site
state: Nebraska
city: Howell
country: United States
facility: Chiesi Investigational Site
state: New Jersey
city: New Brunswick
country: United States
facility: Chiesi Investigational Site
state: New Jersey
city: Durham
country: United States
facility: Chiesi Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Chiesi Investigational Site
state: North Carolina
city: Toledo
country: United States
facility: Chiesi Investigational Site
state: Ohio
city: Toledo
country: United States
facility: Chiesi Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Chiesi Investigational Site
state: Oklahoma
city: Bend
country: United States
facility: Chiesi Investigational Site
state: Oregon
city: Portland
country: United States
facility: Chiesi Investigational Site
state: Oregon
city: Bethlehem
country: United States
facility: Chiesi Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Chiesi Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: Chiesi Investigational Site
state: South Carolina
city: Franklin
country: United States
facility: Chiesi Investigational Site
state: Tennessee
city: Knoxville
country: United States
facility: Chiesi Investigational Site
state: Tennessee
city: Fredericksburg
country: United States
facility: Chiesi Investigational Site
state: Virginia
city: Lynchburg
country: United States
facility: Chiesi Investigational Site
state: Virginia
city: Mar del Plata
country: Argentina
facility: Chiesi Investigational Site
state: Buenos Aires
city: Villa Maria
country: Argentina
facility: Chiesi Investigational Site
state: Cordoba
city: Rosario
country: Argentina
facility: Chiesi Investigational Site
state: Santa Fe
city: Cordoba
country: Argentina
facility: Chiesi Investigational Site
city: Cordoba
country: Argentina
facility: Chiesi Investigational Site
city: Cordoba
country: Argentina
facility: Chiesi Investigational Site
city: Cordoba
country: Argentina
facility: Chiesi Investigational Site
city: Salta
country: Argentina
facility: Chiesi Investigational Site
city: Salta
country: Argentina
facility: Chiesi Investigational Site
city: San Juan
country: Argentina
facility: Chiesi Investigational Site
city: Arlon
country: Belgium
facility: Chiesi Investigational Site
city: Bonheiden
country: Belgium
facility: Chiesi Investigational Site
city: Brugge
country: Belgium
facility: Chiesi Investigational Site
city: Gent
country: Belgium
facility: Chiesi Investigational Site
city: Hasselt
country: Belgium
facility: Chiesi Investigational Site
city: Kortrijk
country: Belgium
facility: Chiesi Investigational Site
city: Mechelen
country: Belgium
facility: Chiesi Investigational Site
city: Roeselare
country: Belgium
facility: Chiesi Investigational Site
city: Brno
country: Czechia
facility: Chiesi Investigational Site
city: Brno
country: Czechia
facility: Chiesi Investigational Site
city: Plzen
country: Czechia
facility: Chiesi Investigational Site
city: Praha 10
country: Czechia
facility: Chiesi Investigational Site
city: Praha 2
country: Czechia
facility: Chiesi Investigational Site
city: Praha 5
country: Czechia
facility: Chiesi Investigational Site
city: Slany
country: Czechia
facility: Chiesi Investigational Site
city: Gdansk
country: Poland
facility: Chiesi Investigational Site
city: Katowice
country: Poland
facility: Chiesi Investigational Site
city: Poznan
country: Poland
facility: Chiesi Investigational Site
city: Skawina
country: Poland
facility: Chiesi Investigational Site
city: Tomaszow Mazowiecki
country: Poland
facility: Chiesi Investigational Site
city: Wegrow
country: Poland
facility: Chiesi Investigational Site
city: Bucuresti
country: Romania
facility: Chiesi Investigational Site
city: Bucuresti
country: Romania
facility: Chiesi Investigational Site
city: Cluj-Napoca
country: Romania
facility: Chiesi Invesitgational Site
city: Constanta
country: Romania
facility: Chiesi Investigational Site
city: Craiova
country: Romania
facility: Chiesi Investigational Site
city: Craiova
country: Romania
facility: Chiesi Investigational Site
city: Targu Mures
country: Romania
facility: Chiesi Investigational Site
city: Terrassa
country: Spain
facility: Chiesi Investigational Site
state: Barcelona
city: Barcelona
country: Spain
facility: Chiesi Investigational Site
city: Barcelona
country: Spain
facility: Chiesi Investigational Site
city: Sevilla
country: Spain
facility: Chiesi Investigational Site
Study officials:
References: