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

(READY1 Trial)

Recruiting at 67 trial locations

Overseen By Chiesi Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Chiesi Farmaceutici S.p.A.

Must not be taking: Fibrinolytics, Anticoagulants

Disqualifiers: Hemodialysis, Infection, Bleeding risk, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 1 day

462 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not use any fibrinolytic agents or anticoagulants (like alteplase, tenecteplase, reteplase, urokinase, or heparin) within 24 hours before starting the study treatment. However, using subcutaneous low molecular weight heparin for preventing blood clots is allowed.

Is alteplase (t-PA) generally safe for humans?

Alteplase, also known as t-PA, has been used for many years to treat conditions like heart attacks and strokes. It is generally considered safe, but it can increase the risk of bleeding, so it should not be used in people with active internal bleeding or conditions that could lead to serious bleeding. ^{1 2 3 4 5}

How is the drug Alteplase (CUSA-081) unique compared to other treatments for acute ischemic stroke?

Alteplase is unique because it is the first and only approved thrombolytic drug for acute ischemic stroke in the UK, working by dissolving blood clots to restore blood flow to the brain. It is administered intravenously and is specifically designed to target fibrin, a protein involved in clot formation, making it more effective in clot dissolution compared to other treatments. ^{2 3 4 5 6}

What is the purpose of this trial?

This trial tests CUSA-081 to see if it can fix medical devices used for accessing veins in adults. The goal is to restore the function of these devices by clearing issues.

Eligibility Criteria

Inclusion Criteria

Inability to have 3mL of blood withdrawn from the selected study catheter;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

Exclusion Criteria

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)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive 1 or 2 doses of study drug (CUSA-081, placebo, or alteplase) directly into the catheter lumen

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events and recurrent catheter dysfunction

30 days

1 visit (in-person) on Day 30

Treatment Details

Interventions

• Alteplase
• CUSA-081
• Placebo

Participant Groups

Group I: CUSA-081 Experimental Treatment 1 Intervention

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.

Group II: Alteplase Active Control 1 Intervention

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.

Group III: Placebo Placebo Group 1 Intervention

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.

Alteplase is already approved in United States, European Union for the following indications:

Approved in United States as Activase for:

• Acute ischemic stroke
• Acute myocardial infarction
• Pulmonary embolism
• Blocked central venous catheter

Approved in European Union as Actilyse for:

• Acute ischemic stroke
• Acute myocardial infarction
• Pulmonary embolism
• Blocked central venous catheter

Who Is Running the Clinical Trial?

Chiesi Farmaceutici S.p.A.

Lead Sponsor

Trials

206

Recruited

315,000+

Founded

1935

Headquarters

Parma, Italy

Known For

Respiratory diseases

Top Products

NEXThaler, Trimbow, Curosurf, Holoclar

Findings from Research

Fibrinolytic agents, like alteplase, have maintained similar efficacy and safety profiles for nearly 20 years, indicating their established role in treatment.

Newer fibrinolytic agents offer longer half-lives, which improve their delivery, yet fibrinolytic therapy remains underutilized, particularly in high-risk patients who could benefit from it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New fibrinolytic agents for MI: as effective as current agents, but easier to administer. Ellis, K., Brener, S.[2019]

In the GUSTO-III trial involving 15,059 patients, both reteplase (r-PA) and tissue plasminogen activator (t-PA) showed similar mortality rates at 1 year, with 11.06% for t-PA and 11.20% for r-PA, indicating comparable efficacy in treating occluded coronary arteries.

The study revealed a concerning increase in mortality rates from 30 days to 1 year compared to previous trials, suggesting that the current patient population may be at higher risk and emphasizing the need for better secondary prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial. Topol, EJ., Ohman, EM., Armstrong, PW., et al.[2019]

Recombinant tissue plasminogen activator (rt-PA) is the only licensed thrombolytic treatment for acute ischemic stroke in the UK, highlighting its importance in emergency stroke care.

The use of rt-PA can improve long-term clinical outcomes for selected patients when integrated into a comprehensive stroke management service.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thrombolytic therapy for acute ischaemic stroke. Jenkinson, D.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

New fibrinolytic agents for MI: as effective as current agents, but easier to administer. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Methodology for the Canadian Activase for Stroke Effectiveness Study (CASES). CASES Investigators. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Alteplase: a tissue plasminogen activator for acute myocardial infarction. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Thrombolytic therapy for acute ischaemic stroke. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

The effect of the one-chain to two-chain conversion in tissue plasminogen activator: characterization of mutations at position 275. [2019]