Efficacy and Safety of CUSA-081 in the Restoration of Cen... | NCT03594175

ID	Type	Description	Link
2019-002124-32	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
CUSA-081	Drug	Participants received 1 or 2 doses of CUSA-081 0.7 mg/2 mL directly into the catheter lumen	CUSA-081

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Facility	Status	City	State	ZIP	Country	Contacts
Chiesi Investigational Site		Little Rock	Arkansas	72205	United States
Chiesi Investigational Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 21, 2023	Jun 10, 2024

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title	Denominators	Categories
Age categorical	ParticipantsBG000253 ParticipantsBG00127 ParticipantsBG002168 ParticipantsBG003

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG000253 ParticipantsBG00127 ParticipantsBG002

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000253 ParticipantsBG00127 ParticipantsBG002

Ethnicity (NIH/OMB)

In some countries (e.g. Belgium) it is against the national law to collect information on ethnicity.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000177 ParticipantsBG00118 ParticipantsBG002

Race (NIH/OMB)

In some countries (e.g. Belgium) it is against the national law to collect information on race.

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000177 ParticipantsBG00118 ParticipantsBG002

Body mass index

Body mass index (BMI) is a measure of body fat based on height and weight that applies to adult men and women.

Mean

Standard Deviation

kg/m^2

Title	Denominators	Categories
	ParticipantsBG000253 ParticipantsBG00127 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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%.

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).

Posted

Count of Participants

Participants

Day 1 (up to 90 mins post dose)

ID	Title	Description
OG000	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
OG001	Placebo	Participants received 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. Placebo: Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen

Units	Counts
Participants	OG000253 OG00127

Title

Denominators

Categories

Title	Measurements
	OG000159 OG0019

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	CUSA-081 vs Placebo Dwell Time Up To 90 Min -- FAS	2-sample Z test for proportions		0.003		Mean difference of proportions, Wald	29.51			2-Sided	95	10.76	48.26					Superiority

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)

The PP set was used for sensitivity analysis when testing for non-inferiority.

Per protocol (PP) set included all subjects from the SAF without any important protocol deviations.

Posted

Count of Participants

Participants

Day 1 (up to 90 min post dose)

ID	Title	Description
OG000	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
OG001	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

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)

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%.

Posted

Count of Participants

Participants

Day 1 (up to 60 min post dose)

ID	Title	Description
OG000	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
OG001	Placebo	Participants received 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. Placebo: Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen

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.

Posted

Count of Participants

Participants

Day 1 (up to 180 min post dose)

ID	Title	Description
OG000	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

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%.

Posted

Count of Participants

Participants

Day 1 (up to 90 min post dose)

ID	Title	Description
OG000	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
OG001	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

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.

Posted

Count of Participants

Participants

Day 1 (post dose) up to Day 30

ID	Title	Description
OG000	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
OG001	Placebo

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'.

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.

Posted

Number

% of subjects with at least one event

Day 1 (start of treatment) and until the end of the treatment period (up to 180 min post dose).

ID	Title	Description
OG000	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
OG001	Placebo	Participants received 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. Placebo: Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen
OG002

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.

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.

Posted

Number

% of subjects with at least one event

Day 1 (start of treatment) and until the end of the treatment period (up to 180 min post dose).

ID	Title	Description
OG000	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
OG001	Placebo	Participants received 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. Placebo: Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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	253	8	253
EG001	Placebo	Participants received 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. Placebo: Participants received 1 or 2 doses of placebo (normal saline) directly into the catheter lumen	27	27	0	27
EG002	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	168	1	168

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected253 at risk EG0010 events0 affected27 at risk EG0020 events0 affected168 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected253 at risk EG0010 events0 affected27 at risk EG0020 events0 affected168 at risk
Sinusitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected253 at risk EG0010 events0 affected27 at risk EG0020 events0 affected168 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected253 at risk EG0010 events0 affected27 at risk EG0020 events0 affected168 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected253 at risk EG0010 events0 affected27 at risk EG0020 events0 affected168 at risk
Polyneuropathy	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected253 at risk EG0010 events0 affected27 at risk EG0021 events1 affected168 at risk
Device breakage	Product Issues	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected253 at risk EG0010 events0 affected27 at risk EG0020 events0 affected168 at risk
Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected253 at risk EG0010 events0 affected27 at risk EG0020 events0 affected168 at risk

Certain Agreements

ID	Term
D013927	Thrombosis
D001733	Bites and Stings

ID	Term
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D011041	Poisoning
D064419	Chemically-Induced Disorders
D014947	Wounds and Injuries

ID	Term
D012697	Serine Endopeptidases
D010450	Endopeptidases
D010447	Peptide Hydrolases
D006867	Hydrolases
D004798	Enzymes
D045762	Enzymes and Coenzymes
D057057	Serine Proteases
D010960	Plasminogen Activators
D001779	Blood Coagulation Factors
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D001685	Biological Factors