READY 1: Efficacy and Safety of CUSA-081 in the Restoration of Central Venous Access Device (CVAD) Functionality

Sponsor
Chiesi Farmaceutici S.p.A. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03594175
Collaborator
(none)
800
77
3
67.6
10.4
0.2

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
800 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Feb 12, 2020
Anticipated Primary Completion Date :
Feb 1, 2025
Anticipated Study Completion Date :
Oct 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: CUSA-081

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

Drug: CUSA-081
Participants will receive 1 or 2 doses of CUSA-081 0.7 mg/2 mL directly into the catheter lumen
Other Names:
  • reteplase
  • Placebo Comparator: Placebo

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

    Drug: Placebo
    Participants will receive 1 or 2 doses of placebo (normal saline) directly into the catheter lumen

    Active Comparator: Alteplase

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

    Drug: Alteplase
    Participants will receive 1 or 2 doses of alteplase, 2 mg/2 mL, directly into the catheter lumen

    Outcome Measures

    Primary Outcome Measures

    1. Percentage Of Participants With Treatment Success Following A Single Instillation Of Study Drug With A Dwell Time Up To 90 Mins [Day 1 (up to 90 mins postdose)]

      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%.

    Secondary Outcome Measures

    1. Percentage Of Participants With Treatment Success Following A Single Instillation Of Study Drug With A Total Dwell Time Up To 30 And 60 Mins [Day 1 (up to 30 and 60 mins postdose)]

      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%.

    2. 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 [Day 1 (up to 120, 150, and 180 mins postdose)]

      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%.

    3. Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug [Day 1 (postdose) up to Day 30]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Chiesi Investigational Site Little Rock Arkansas United States 72205
    2 Chiesi Investigational Site Redlands California United States 92373
    3 Chiesi Investigational Site Stockton California United States 95204
    4 Chiesi Investigational Site Norwich Connecticut United States 06360
    5 Chiesi Investigational Site Newark Delaware United States 19718
    6 Chiesi Investigational Site Jacksonville Florida United States 32209
    7 Chiesi Investigational Site Miami Florida United States 33155-3009
    8 Chiesi Investigational Site Plantation Florida United States 33322
    9 Chiesi Investigational Site Weeki Wachee Florida United States 34607
    10 Chiesi Investigational Site Weston Florida United States 33331
    11 Chiesi Investigational Site Atlanta Georgia United States 30322
    12 Chiesi Investigational Site Honolulu Hawaii United States 96814
    13 Chiesi Investigational Site Quincy Illinois United States 62301
    14 Chiesi Investigational Site New Albany Indiana United States 47150
    15 Einspahr Topeka Kansas United States 66606
    16 Chiesi Investigational Site Lewiston Maine United States 04240
    17 Chiesi Investigational Site Hannibal Missouri United States 63401
    18 Chiesi Investigational Site Kalispell Montana United States 59901-3158
    19 Chiesi Investigational Site Omaha Nebraska United States 68131
    20 Chiesi Investigational Site Howell New Jersey United States 07731
    21 Chiesi Investigational Site New Brunswick New Jersey United States 08901
    22 Chiesi Investigational Site Durham North Carolina United States 27710
    23 Chiesi Investigational Site Winston-Salem North Carolina United States 27103
    24 Chiesi Investigational Site Toledo Ohio United States 43608
    25 Chiesi Investigational Site Toledo Ohio United States 43614
    26 Chiesi Investigational Site Oklahoma City Oklahoma United States 73104
    27 Chiesi Investigational Site Bend Oregon United States 97701
    28 Chiesi Investigational Site Portland Oregon United States 97210
    29 Chiesi Investigational Site Bethlehem Pennsylvania United States 18015
    30 Chiesi Investigational Site Charleston South Carolina United States 29414
    31 Chiesi Investigational Site Spartanburg South Carolina United States 29303
    32 Chiesi Investigational Site Franklin Tennessee United States 37067
    33 Chiesi Investigational Site Knoxville Tennessee United States 37920
    34 Chiesi Investigational Site Fredericksburg Virginia United States 22401
    35 Chiesi Investigational Site Lynchburg Virginia United States 24501
    36 Chiesi Investigational Site Mar del Plata Buenos Aires Argentina B7600FYK
    37 Chiesi Investigational Site Villa Maria Cordoba Argentina X5900JKA
    38 Chiesi Investigational Site Rosario Santa Fe Argentina S2000DIF
    39 Chiesi Investigational Site Cordoba Argentina 5000
    40 Chiesi Investigational Site Cordoba Argentina X5000JHQ
    41 Chiesi Investigational Site Cordoba Argentina X5002AOQ
    42 Chiesi Investigational Site Cordoba Argentina X5021FPQ
    43 Chiesi Investigational Site Salta Argentina A4400ANW
    44 Chiesi Investigational Site Salta Argentina A4400
    45 Chiesi Investigational Site San Juan Argentina 5400
    46 Chiesi Investigational Site Arlon Belgium 6700
    47 Chiesi Investigational Site Bonheiden Belgium 2820
    48 Chiesi Investigational Site Brugge Belgium 8000
    49 Chiesi Investigational Site Gent Belgium 9000
    50 Chiesi Investigational Site Hasselt Belgium 3500
    51 Chiesi Investigational Site Kortrijk Belgium 8500
    52 Chiesi Investigational Site Mechelen Belgium 2800
    53 Chiesi Investigational Site Roeselare Belgium 8800
    54 Chiesi Investigational Site Brno Czechia 625 00
    55 Chiesi Investigational Site Brno Czechia 656 91
    56 Chiesi Investigational Site Plzen Czechia 305 99
    57 Chiesi Investigational Site Praha 10 Czechia 10034
    58 Chiesi Investigational Site Praha 2 Czechia 128 08
    59 Chiesi Investigational Site Praha 5 Czechia 150 06
    60 Chiesi Investigational Site Slany Czechia 274 01
    61 Chiesi Investigational Site Gdansk Poland 80-803
    62 Chiesi Investigational Site Katowice Poland 40-027
    63 Chiesi Investigational Site Poznan Poland 61-866
    64 Chiesi Investigational Site Skawina Poland 32-050
    65 Chiesi Investigational Site Tomaszow Mazowiecki Poland 97-200
    66 Chiesi Investigational Site Wegrow Poland 07-100
    67 Chiesi Investigational Site Bucuresti Romania 021659
    68 Chiesi Investigational Site Bucuresti Romania 022328
    69 Chiesi Invesitgational Site Cluj-Napoca Romania 400006
    70 Chiesi Investigational Site Constanta Romania 900591
    71 Chiesi Investigational Site Craiova Romania 200347
    72 Chiesi Investigational Site Craiova Romania 200640
    73 Chiesi Investigational Site Targu Mures Romania 40103
    74 Chiesi Investigational Site Terrassa Barcelona Spain 08221
    75 Chiesi Investigational Site Barcelona Spain 08041
    76 Chiesi Investigational Site Barcelona Spain 8035
    77 Chiesi Investigational Site Sevilla Spain 41009

    Sponsors and Collaborators

    • Chiesi Farmaceutici S.p.A.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Chiesi Farmaceutici S.p.A.
    ClinicalTrials.gov Identifier:
    NCT03594175
    Other Study ID Numbers:
    • CUSA-081-HEM-01
    • 2019-002124-32
    First Posted:
    Jul 20, 2018
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Chiesi Farmaceutici S.p.A.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 31, 2022