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

NCT03594175 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: CUSA-081-HEM-012019-002124-32
• Study Type: interventional
• Target: 462
• Locations: 7 countries
• Sites: 77

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.

Conditions

Catheter Occlusion; Thrombosis

Keywords

Central Venous Access Device (CVAD); CUSA-081; reteplase; alteplase; occluded catheters; catheter; occlusion; thrombosis; thrombotic occlusion; CVAD

Outcome Measures

Primary Outcomes (1)

• 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%.

  Day 1 (up to 90 mins post dose)

Secondary Outcomes (7)

• 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)

  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)

  Day 1 (up to 60 min post dose)

• 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)

  Day 1 (up to 180 min post dose)

• 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)

  Day 1 (up to 90 min post dose)

• Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug

  Day 1 (post dose) up to Day 30

Study Arms (3)

CUSA-081

EXPERIMENTAL

Participants received 1 or 2 doses of CUSA-081, 0.7 milligrams (mg) (0.4 units) per 2 milliliter (mL) directly into the catheter lumen. Participants received the first dose at minute (min) 0, and the second dose (if needed) at min 90.

Drug: CUSA-081

Placebo

PLACEBO COMPARATOR

Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen. Participants received the first dose at min 0, and the second dose (if needed) at min 90.

Drug: Placebo

Alteplase

ACTIVE COMPARATOR

Participants received 1 or 2 doses of alteplase, 2 mg/mL, directly into the catheter lumen. Participants received the first dose at min 0, and the second dose (if needed) at min 90.

Drug: Alteplase

Interventions

CUSA-081 DRUG

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

Also known as: Reteplase

CUSA-081

Placebo DRUG

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

Placebo

Alteplase DRUG

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

Alteplase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Inability to have 3 mL of blood withdrawn from the selected study catheter;
• 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;
• 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;
• Male and non-pregnant female subjects from all racial and ethnic groups 18 years of age and older;
• Able to have fluids infused at the volume necessary to instil study drug into the CVAD (i.e., up to 2 mL);
• 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.

You may not qualify if:

• CVAD (any type) used for hemodialysis;
• CVAD known to be dysfunctional for more than 48 hours;
• 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;
• Known or suspected catheter related bloodstream infection (CRBSI);
• 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;
• 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);
• Uncontrolled hypertension (systolic BP ≥160 or diastolic BP ≥110 mmHg) at screening;
• Clinically unstable in the opinion of the site investigator;
• Known to be pregnant or breastfeeding at screening;
• Previously treated in this study (READY 1) or in study READY 2;
• History of allergic reaction to reteplase, alteplase or vial ingredients (excipients or diluents);
• Use of any investigational drug or experimental medical device within 28 days prior to treatment; 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.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (77)

Chiesi Investigational Site

Little Rock, Arkansas, 72205, United States

Location

Chiesi Investigational Site

Redlands, California, 92373, United States

Location

Chiesi Investigational Site

Stockton, California, 95204, United States

Location

Chiesi Investigational Site

Norwich, Connecticut, 06360, United States

Location

Chiesi Investigational Site

Newark, Delaware, 19718, United States

Location

Chiesi Investigational Site

Jacksonville, Florida, 32209, United States

Location

Chiesi Investigational Site

Miami, Florida, 33155-3009, United States

Location

Chiesi Investigational Site

Plantation, Florida, 33322, United States

Location

Chiesi Investigational Site

Weeki Wachee, Florida, 34607, United States

Location

Chiesi Investigational Site

Weston, Florida, 33331, United States

Location

Chiesi Investigational Site

Atlanta, Georgia, 30322, United States

Location

Chiesi Investigational Site

Honolulu, Hawaii, 96814, United States

Location

Chiesi Investigational Site

Quincy, Illinois, 62301, United States

Location

Chiesi Investigational Site

New Albany, Indiana, 47150, United States

Location

Einspahr

Topeka, Kansas, 66606, United States

Location

Chiesi Investigational Site

Lewiston, Maine, 04240, United States

Location

Chiesi Investigational Site

Hannibal, Missouri, 63401, United States

Location

Chiesi Investigational Site

Kalispell, Montana, 59901-3158, United States

Location

Chiesi Investigational Site

Omaha, Nebraska, 68131, United States

Location

Chiesi Investigational Site

Howell Township, New Jersey, 07731, United States

Location

Chiesi Investigational Site

New Brunswick, New Jersey, 08901, United States

Location

Chiesi Investigational Site

Durham, North Carolina, 27710, United States

Location

Chiesi Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

Chiesi Investigational Site

Toledo, Ohio, 43608, United States

Location

Chiesi Investigational Site

Toledo, Ohio, 43614, United States

Location

Chiesi Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

Chiesi Investigational Site

Bend, Oregon, 97701, United States

Location

Chiesi Investigational Site

Portland, Oregon, 97210, United States

Location

Chiesi Investigational Site

Bethlehem, Pennsylvania, 18015, United States

Location

Chiesi Investigational Site

Charleston, South Carolina, 29414, United States

Location

Chiesi Investigational Site

Spartanburg, South Carolina, 29303, United States

Location

Chiesi Investigational Site

Franklin, Tennessee, 37067, United States

Location

Chiesi Investigational Site

Knoxville, Tennessee, 37920, United States

Location

Chiesi Investigational Site

Fredericksburg, Virginia, 22401, United States

Location

Chiesi Investigational Site

Lynchburg, Virginia, 24501, United States

Location

Chiesi Investigational Site

Mar del Plata, Buenos Aires, B7600FYK, Argentina

Location

Chiesi Investigational Site

Villa María, Córdoba Province, X5900JKA, Argentina

Location

Chiesi Investigational Site

Rosario, Santa Fe Province, S2000DIF, Argentina

Location

Chiesi Investigational Site

Córdoba, 5000, Argentina

Location

Chiesi Investigational Site

Córdoba, X5000JHQ, Argentina

Location

Chiesi Investigational Site

Córdoba, X5002AOQ, Argentina

Location

Chiesi Investigational Site

Córdoba, X5021FPQ, Argentina

Location

Chiesi Investigational Site

Salta, A4400ANW, Argentina

Location

Chiesi Investigational Site

Salta, A4400, Argentina

Location

Chiesi Investigational Site

San Juan, 5400, Argentina

Location

Chiesi Investigational Site

Arlon, 6700, Belgium

Location

Chiesi Investigational Site

Bonheiden, 2820, Belgium

Location

Chiesi Investigational Site

Bruges, 8000, Belgium

Location

Chiesi Investigational Site

Ghent, 9000, Belgium

Location

Chiesi Investigational Site

Hasselt, 3500, Belgium

Location

Chiesi Investigational Site

Kortrijk, 8500, Belgium

Location

Chiesi Investigational Site

Mechelen, 2800, Belgium

Location

Chiesi Investigational Site

Roeselare, 8800, Belgium

Location

Chiesi Investigational Site

Brno, 625 00, Czechia

Location

Chiesi Investigational Site

Brno, 656 91, Czechia

Location

Chiesi Investigational Site

Pilsen, 305 99, Czechia

Location

Chiesi Investigational Site

Prague, 10034, Czechia

Location

Chiesi Investigational Site

Prague, 128 08, Czechia

Location

Chiesi Investigational Site

Prague, 150 06, Czechia

Location

Chiesi Investigational Site

Slaný, 274 01, Czechia

Location

Chiesi Investigational Site

Gdansk, 80-803, Poland

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Chiesi Investigational Site

Katowice, 40-027, Poland

Location

Chiesi Investigational Site

Poznan, 61-866, Poland

Location

Chiesi Investigational Site

Skawina, 32-050, Poland

Location

Chiesi Investigational Site

Tomaszów Mazowiecki, 97-200, Poland

Location

Chiesi Investigational Site

Węgrów, 07-100, Poland

Location

Chiesi Investigational Site

Bucharest, 021659, Romania

Location

Chiesi Investigational Site

Bucharest, 022328, Romania

Location

Chiesi Invesitgational Site

Cluj-Napoca, 400006, Romania

Location

Chiesi Investigational Site

Constanța, 900591, Romania

Location

Chiesi Investigational Site

Craiova, 200347, Romania

Location

Chiesi Investigational Site

Craiova, 200640, Romania

Location

Chiesi Investigational Site

Târgu Mureş, 40103, Romania

Location

Chiesi Investigational Site

Terrassa, Barcelona, 08221, Spain

Location

Chiesi Investigational Site

Barcelona, 08041, Spain

Location

Chiesi Investigational Site

Barcelona, 8035, Spain

Location

Chiesi Investigational Site

Seville, 41009, Spain

Location

MeSH Terms

Conditions

Thrombosis; Bites and Stings

Interventions

reteplase; Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Limitations and Caveats

13 June 2023, Chiesi issued an initial notification of enrolment hold to all participating study sites for READY 1 study. 05 July 2023, Chiesi issued a voluntary official notification of early termination of study recruitment to all participating sites, due to non-safety reasons. Patient recruitment was slow and completion of the study was not feasible in a reasonable timeframe. Early termination of the study was not expected to impact patient access to other necessary treatments.

Results Point of Contact

• Title: Clinical Trial Transparency
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

+ 39 0521 2791

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: July 20, 2018
• Study Start: February 12, 2020
• Primary Completion: June 8, 2023
• Study Completion: July 10, 2023
• Last Updated: August 23, 2024
• Results First Posted: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

RO (7); ES (4); BE (8); US (35); AR (10); CZ (7); PL (6)