Catheter Occlusion, Thrombosis
Conditions
Keywords
Central Venous Access Device (CVAD), CUSA-081, reteplase, alteplase, occluded catheters, catheter, occlusion, thrombosis, thrombotic occlusion, CVAD
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.
Interventions
DRUGCUSA-081
Participants received 1 or 2 doses of CUSA-081 0.7 mg/2 mL directly into the catheter lumen
DRUGPlacebo
Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen
DRUGAlteplase
Participants received 1 or 2 doses of alteplase, 2 mg/2 mL, directly into the catheter lumen
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Day 1 (up to 90 mins post dose) | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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%. |
| 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) | CUSA-081 vs Placebo -- 2 Instillations of study drug -- Dwell Time Up To 180 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 180 mins, following 2 installations of the 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%. Subjects received the first instillation of study drug (CUSA-081, placebo, or alteplase). If patency was not restored after 90 minutes following the first instillation, a second dose of study drug (the same drug as at first instillation) was administered. |
| 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) | CUSA-081 vs Alteplase -- 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 is 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%. |
| 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) | 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. |
| Percentage of Participants With Treatment-emergent Adverse Events (AEs) Leading to Study Discontinuation | Day 1 (start of treatment) and until the end of the treatment period (up to 180 min post dose). | Treatment-emergent AEs leading to study discontinuation were evaluated and the percentage of participants with at least one event reported. For all subjects who discontinued the study, the AE was 'Device breakage'. |
| Percentage of Participants With Treatment-emergent Adverse Events (AEs) of Special Interest (AESI) | Day 1 (start of treatment) and until the end of the treatment period (up to 180 min post dose). | Treatment-emergent AEs of special interest (AESI) were monitored. These included major bleeding (defined as severe blood loss \[\>5 mL/kg\] or blood loss requiring transfusion or causing hypotension requiring use of inotropic agents), embolism, thrombosis, and catheter-related blood stream infection. An adverse event was considered as treatment-emergent if it started on or after the first dose of study drug intake up to the end of the 180-minute treatment period. |
| Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug | Day 1 (post dose) up to Day 30 | The rate of recurrent catheter dysfunction is defined as re-occlusion. The rate of recurrent catheter dysfunction within 30 days following treatment and the results of the Kaplan-Meier and Cox proportional hazards analyses of the time to first re-occlusion are presented in the FAS. 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 min. Subjects received the first instillation of study drug (CUSA-081, placebo, or alteplase). If patency was not restored after 90 minutes following the first instillation, a second dose of study drug (the same drug as at first instillation) was administered. |
Countries
Argentina, Belgium, Czechia, Poland, Romania, Spain, United States
Participant flow
Pre-assignment details
Subjects who qualified for the study after completing of all screening assessments were randomized to treatment groups and received the randomized study drug.
Participants by arm
| Arm | Count |
|---|---|
| CUSA-081 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.
CUSA-081: Participants received 1 or 2 doses of CUSA-081 0.7 mg/2 mL directly into the catheter lumen. | 253 |
| Placebo 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.
Placebo: Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen. | 27 |
| Alteplase 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.
Alteplase: Participants received 1 or 2 doses of alteplase, 2 mg/2 mL, directly into the catheter lumen. | 168 |
| Total | 448 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 0 |
| Overall Study | Not treated | 8 | 1 | 5 |
| Overall Study | Protocol Violation | 2 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | CUSA-081 | Placebo | Alteplase | Total |
|---|---|---|---|---|
| Age, Categorical Age categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Age categorical >=65 years | 113 Participants | 12 Participants | 74 Participants | 199 Participants |
| Age, Categorical Age categorical Between 18 and 65 years | 140 Participants | 15 Participants | 94 Participants | 249 Participants |
| Age, Continuous | 60.6 years STANDARD_DEVIATION 13.5 | 60.4 years STANDARD_DEVIATION 12.7 | 60.9 years STANDARD_DEVIATION 14.3 | 60.7 years STANDARD_DEVIATION 13.7 |
| Body mass index | 28.05 kg/m^2 STANDARD_DEVIATION 6.49 | 27.75 kg/m^2 STANDARD_DEVIATION 5.62 | 28.01 kg/m^2 STANDARD_DEVIATION 6.11 | 28.02 kg/m^2 STANDARD_DEVIATION 6.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 7 Participants | 24 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants | 9 Participants | 101 Participants | 242 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 0 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 166 Participants | 17 Participants | 119 Participants | 302 Participants |
| Sex: Female, Male Female | 150 Participants | 16 Participants | 103 Participants | 269 Participants |
| Sex: Female, Male Male | 103 Participants | 11 Participants | 65 Participants | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 253 | 0 / 27 | 0 / 168 |
| other Total, other adverse events | 8 / 253 | 0 / 27 | 1 / 168 |
| serious Total, serious adverse events | 0 / 253 | 0 / 27 | 0 / 168 |
Outcome results
Primary
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)
Population: Full analysis set (FAS) was used for the analysis. FAS included all randomized subjects who received at least one dose of study drug, and with at least one available evaluation of efficacy after baseline (i.e., at least one CVAD assessment after study drug administration).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CUSA-081 | 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) | 159 Participants |
| Placebo | 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) | 9 Participants |
Comparison: CUSA-081 vs Placebo Dwell Time Up To 90 Min -- FASp-value: 0.00395% CI: [10.76, 48.26]2-sample Z test for proportions
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (AEs) Leading to Study Discontinuation
Treatment-emergent AEs leading to study discontinuation were evaluated and the percentage of participants with at least one event reported. For all subjects who discontinued the study, the AE was 'Device breakage'.
Time frame: Day 1 (start of treatment) and until the end of the treatment period (up to 180 min post dose).
Population: The safety set (SAF) included all randomized subjects who received at least one dose of study drug. Subjects discontinued after dosing were included in the SAF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CUSA-081 | Percentage of Participants With Treatment-emergent Adverse Events (AEs) Leading to Study Discontinuation | 1.2 % of subjects with at least one event |
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (AEs) Leading to Study Discontinuation | 0 % of subjects with at least one event |
| Alteplase | Percentage of Participants With Treatment-emergent Adverse Events (AEs) Leading to Study Discontinuation | 0 % of subjects with at least one event |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (AEs) of Special Interest (AESI)
Treatment-emergent AEs of special interest (AESI) were monitored. These included major bleeding (defined as severe blood loss \[\>5 mL/kg\] or blood loss requiring transfusion or causing hypotension requiring use of inotropic agents), embolism, thrombosis, and catheter-related blood stream infection. An adverse event was considered as treatment-emergent if it started on or after the first dose of study drug intake up to the end of the 180-minute treatment period.
Time frame: Day 1 (start of treatment) and until the end of the treatment period (up to 180 min post dose).
Population: The safety set (SAF) included all randomized subjects who received at least one dose of study drug. Subjects discontinued after dosing were included in the SAF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CUSA-081 | Percentage of Participants With Treatment-emergent Adverse Events (AEs) of Special Interest (AESI) | 0 % of subjects with at least one event |
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (AEs) of Special Interest (AESI) | 0 % of subjects with at least one event |
| Alteplase | Percentage of Participants With Treatment-emergent Adverse Events (AEs) of Special Interest (AESI) | 0 % of subjects with at least one event |
Secondary
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)
CUSA-081 vs Placebo -- 2 Instillations of study drug -- Dwell Time Up To 180 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 180 mins, following 2 installations of the 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%. Subjects received the first instillation of study drug (CUSA-081, placebo, or alteplase). If patency was not restored after 90 minutes following the first instillation, a second dose of study drug (the same drug as at first instillation) was administered.
Time frame: Day 1 (up to 180 min post dose)
Population: Full analysis set (FAS) was used for the analysis. FAS included all randomized subjects who received at least one dose of study drug, and with at least one available evaluation of efficacy after baseline (i.e., at least one CVAD assessment after study drug administration).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CUSA-081 | 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) | 207 Participants |
| Placebo | 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) | 11 Participants |
p-value: <0.00195% CI: [21.94, 60.21]2-sample Z test for proportions
Secondary
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%.
Time frame: Day 1 (up to 60 min post dose)
Population: Full analysis set (FAS) was used for the analysis. FAS included all randomized subjects who received at least one dose of study drug, and with at least one available evaluation of efficacy after baseline (i.e., at least one CVAD assessment after study drug administration).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CUSA-081 | 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) | 136 Participants |
| Placebo | 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) | 8 Participants |
p-value: 0.01795% CI: [5.84, 42.41]2-sample Z test for proportions
Secondary
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)
CUSA-081 vs Alteplase -- 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 is 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 min post dose)
Population: Full analysis set (FAS) was used for the analysis. FAS included all randomized subjects who received at least one dose of study drug, and with at least one available evaluation of efficacy after baseline (i.e., at least one CVAD assessment after study drug administration).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CUSA-081 | 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) | 159 Participants |
| Placebo | 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) | 124 Participants |
p-value: 0.01995% CI: [-19.89, -2.04]2-sample Z test for proportions
Secondary
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)
Population: Per protocol (PP) set included all subjects from the SAF without any important protocol deviations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CUSA-081 | 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) | 152 Participants |
| Placebo | 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) | 117 Participants |
p-value: 0.0395% CI: [-19.38, -1.24]2-sample Z test for proportions
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 within 30 days following treatment and the results of the Kaplan-Meier and Cox proportional hazards analyses of the time to first re-occlusion are presented in the FAS. 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 min. Subjects received the first instillation of study drug (CUSA-081, placebo, or alteplase). If patency was not restored after 90 minutes following the first instillation, a second dose of study drug (the same drug as at first instillation) was administered.
Time frame: Day 1 (post dose) up to Day 30
Population: Full analysis set (FAS) was used for the analysis. FAS included all randomized subjects who received at least one dose of study drug, and with at least one available evaluation of efficacy after baseline (i.e., at least one CVAD assessment after study drug administration).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CUSA-081 | Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug | 17 Participants |
| Placebo | Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug | 1 Participants |
| Alteplase | Rate Of Recurrent Catheter Dysfunction Within 30 Days Following Treatment With Study Drug | 18 Participants |
Comparison: Time to first re-occlusion.95% CI: [0.126, 7.121]
Comparison: Time to first re-occlusion.95% CI: [0.337, 1.27]
Comparison: Time to first re-occlusion.95% CI: [0.193, 10.848]