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

Thrombosis Clinical Trial

— READY 1  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03594175
• Other study ID #: CUSA-081-HEM-01
• Secondary ID: 2019-002124-32
• Status: Terminated
• Phase: Phase 3
• Start date: February 12, 2020
• Est. completion date: July 10, 2023

Study information

• Verified date: August 2023
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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).

During the study, the treatment period will consist of one visit which may take place on the same day as screening or on the following day. After meeting all inclusion criteria, subjects will be randomized in a 9:1:6 ratio of CUSA-081: placebo: alteplase. There will be a follow-up assessment performed on Day 30 (±2 days) after treatment with study drug.

Routine blood pressure measurement, heart rate and 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 receive study drug in the trial.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 462
• Est. completion date: July 10, 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Inability to have 3mL of blood withdrawn from the selected study catheter;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 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.

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 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.

Related Conditions & MeSH terms

• Catheter Occlusion
• Thrombosis

Intervention

Drug:
• CUSA-081
Participants will receive 1 or 2 doses of CUSA-081 0.7 mg/2 mL directly into the catheter lumen
• Placebo
Participants will receive 1 or 2 doses of placebo (normal saline) directly into the catheter lumen
• Alteplase
Participants will receive 1 or 2 doses of alteplase, 2 mg/2 mL, directly into the catheter lumen

Locations

Country	Name	City	State
Argentina	Chiesi Investigational Site	Cordoba
Argentina	Chiesi Investigational Site	Cordoba
Argentina	Chiesi Investigational Site	Cordoba
Argentina	Chiesi Investigational Site	Cordoba
Argentina	Chiesi Investigational Site	Mar del Plata	Buenos Aires
Argentina	Chiesi Investigational Site	Rosario	Santa Fe
Argentina	Chiesi Investigational Site	Salta
Argentina	Chiesi Investigational Site	Salta
Argentina	Chiesi Investigational Site	San Juan
Argentina	Chiesi Investigational Site	Villa Maria	Cordoba
Belgium	Chiesi Investigational Site	Arlon
Belgium	Chiesi Investigational Site	Bonheiden
Belgium	Chiesi Investigational Site	Brugge
Belgium	Chiesi Investigational Site	Gent
Belgium	Chiesi Investigational Site	Hasselt
Belgium	Chiesi Investigational Site	Kortrijk
Belgium	Chiesi Investigational Site	Mechelen
Belgium	Chiesi Investigational Site	Roeselare
Czechia	Chiesi Investigational Site	Brno
Czechia	Chiesi Investigational Site	Brno
Czechia	Chiesi Investigational Site	Plzen
Czechia	Chiesi Investigational Site	Praha 10
Czechia	Chiesi Investigational Site	Praha 2
Czechia	Chiesi Investigational Site	Praha 5
Czechia	Chiesi Investigational Site	Slany
Poland	Chiesi Investigational Site	Gdansk
Poland	Chiesi Investigational Site	Katowice
Poland	Chiesi Investigational Site	Poznan
Poland	Chiesi Investigational Site	Skawina
Poland	Chiesi Investigational Site	Tomaszow Mazowiecki
Poland	Chiesi Investigational Site	Wegrow
Romania	Chiesi Investigational Site	Bucuresti
Romania	Chiesi Investigational Site	Bucuresti
Romania	Chiesi Invesitgational Site	Cluj-Napoca
Romania	Chiesi Investigational Site	Constanta
Romania	Chiesi Investigational Site	Craiova
Romania	Chiesi Investigational Site	Craiova
Romania	Chiesi Investigational Site	Targu Mures
Spain	Chiesi Investigational Site	Barcelona
Spain	Chiesi Investigational Site	Barcelona
Spain	Chiesi Investigational Site	Sevilla
Spain	Chiesi Investigational Site	Terrassa	Barcelona
United States	Chiesi Investigational Site	Atlanta	Georgia
United States	Chiesi Investigational Site	Bend	Oregon
United States	Chiesi Investigational Site	Bethlehem	Pennsylvania
United States	Chiesi Investigational Site	Charleston	South Carolina
United States	Chiesi Investigational Site	Durham	North Carolina
United States	Chiesi Investigational Site	Franklin	Tennessee
United States	Chiesi Investigational Site	Fredericksburg	Virginia
United States	Chiesi Investigational Site	Hannibal	Missouri
United States	Chiesi Investigational Site	Honolulu	Hawaii
United States	Chiesi Investigational Site	Howell	New Jersey
United States	Chiesi Investigational Site	Jacksonville	Florida
United States	Chiesi Investigational Site	Kalispell	Montana
United States	Chiesi Investigational Site	Knoxville	Tennessee
United States	Chiesi Investigational Site	Lewiston	Maine
United States	Chiesi Investigational Site	Little Rock	Arkansas
United States	Chiesi Investigational Site	Lynchburg	Virginia
United States	Chiesi Investigational Site	Miami	Florida
United States	Chiesi Investigational Site	New Albany	Indiana
United States	Chiesi Investigational Site	New Brunswick	New Jersey
United States	Chiesi Investigational Site	Newark	Delaware
United States	Chiesi Investigational Site	Norwich	Connecticut
United States	Chiesi Investigational Site	Oklahoma City	Oklahoma
United States	Chiesi Investigational Site	Omaha	Nebraska
United States	Chiesi Investigational Site	Plantation	Florida
United States	Chiesi Investigational Site	Portland	Oregon
United States	Chiesi Investigational Site	Quincy	Illinois
United States	Chiesi Investigational Site	Redlands	California
United States	Chiesi Investigational Site	Spartanburg	South Carolina
United States	Chiesi Investigational Site	Stockton	California
United States	Chiesi Investigational Site	Toledo	Ohio
United States	Chiesi Investigational Site	Toledo	Ohio
United States	Einspahr	Topeka	Kansas
United States	Chiesi Investigational Site	Weeki Wachee	Florida
United States	Chiesi Investigational Site	Weston	Florida
United States	Chiesi Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Czechia,  Poland,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Of Participants With Treatment Success Following A Single Instillation Of Study Drug With A Dwell Time Up To 90 Mins	Treatment success is 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 is up to 90 mins. The percentage will be calculated as the number of participants with treatment success divided by the total number of participants in the group, multiplied by 100%.	Day 1 (up to 90 mins postdose)
Secondary	Percentage Of Participants With Treatment Success Following A Single Instillation Of Study Drug With A Total Dwell Time Up To 30 And 60 Mins	Treatment success is 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 is up to 60 mins. The percentage will be calculated as the number of participants with treatment success divided by the total number of participants in the group, multiplied by 100%.	Day 1 (up to 30 and 60 mins postdose)
Secondary	Percentage Of Participants With Treatment Success After Up To 2 Instillations Of Study Drug With A Total Dwell Time Up To 120, 150, And 180 Mins	Treatment success is 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 is up to 180 mins. The percentage will be calculated as the number of participants with treatment success divided by the total number of participants in the group, multiplied by 100%.	Day 1 (up to 120, 150, and 180 mins postdose)
Secondary	Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug	The rate of recurrent catheter dysfunction is defined as re-occlusion. The rate of recurrent catheter dysfunction will be analyzed using the Kaplan-Meier method. This analysis is based on all participants with treatment success following up to 2 administrations of study drug with a total dwell time up to 180 mins.	Day 1 (postdose) up to Day 30