CUSA-081 for Catheter Blockage

(READY1 Trial)

No longer recruiting at 81 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness and safety of a drug called CUSA-081 in unblocking central venous access devices (CVADs), which deliver treatments like medications or nutrients directly into the bloodstream. Participants will receive either the new treatment, a standard treatment called alteplase (a clot-dissolving medication), or a placebo (a substance with no medical effect) to determine which best restores CVAD function. Individuals who have had a CVAD for more than 24 hours and cannot currently draw blood through it might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research is examining the safety of CUSA-081, a diluted form of reteplase. Studies have used it to help unblock devices that access veins, which can sometimes become clogged. These studies aim to determine if CUSA-081 can safely clear these blockages. Although detailed safety information for CUSA-081 isn't widely available yet, its advancement to a late-stage trial suggests promise in earlier research.

Alteplase, however, is already approved for similar uses. It is generally well-tolerated when used to clear blocked catheters, which are thin tubes that deliver treatments directly into veins. Most people don't experience serious side effects, though some may have minor reactions like bleeding or bruising.

Both treatments undergo testing to ensure safety for unblocking devices. This ongoing research helps confirm their effectiveness and safety for use in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment for restoring central venous access device (CVAD) functionality, which typically involves using alteplase, CUSA-081 offers a potentially faster and more efficient solution. Researchers are particularly excited about CUSA-081 because it uses a lower dose (0.7 mg compared to alteplase's 2 mg) to clear blockages in catheters, which could reduce potential side effects and costs. Additionally, its unique formulation may allow it to work quicker, restoring catheter function in a shorter time frame. This new approach could significantly improve patient care by minimizing treatment interruptions and enhancing overall safety and convenience.

What evidence suggests that this trial's treatments could be effective for restoring CVAD functionality?

Research shows that CUSA-081, a diluted form of the drug reteplase, is being tested in this trial to determine its effectiveness in unblocking central venous access devices (CVADs). Reteplase is known for breaking down blood clots, which might help clear blocked catheters. Similar drugs have shown promise in past studies for restoring catheter function, but specific results for CUSA-081 in humans are still being gathered.

This trial also tests alteplase as a treatment option. Strong evidence supports the effectiveness of alteplase, which has successfully cleared catheter blockages in about 66.7% of cases, making it a well-established option for treating blocked catheters. Both treatments in this trial aim to improve catheter use by addressing blockages, but alteplase has more solid support from previous research. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Alteplase
• CUSA-081
• Placebo

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3468107/

Efficacy and Economic Evaluation of a Volume-Based Cathflo ... Our data indicate that the Cathflo Activase protocol may be as efficacious as the previous alteplase protocol. Furthermore, there are added time and cost ...

2. cathflo.com cathflo.com/occluded-catheter/clinical-trials.html

Clinical Trial Results Cathflo® Activase® (alteplase) is integral to evidence-based practices for treating thrombotically occluded catheters · Cumulative efficacy · First dose efficacy.

3. dig.pharmacy.uic.edu dig.pharmacy.uic.edu/faqs/2023-2/february-2023-faqs/what-data-supports-the-use-of-alteplase-1-mg-versus-2-mg-for-catheter-occlusions/

What data supports the use of alteplase 1 mg versus 2 mg for ... Most studies evaluated in this FAQ suggest that dosing of alteplase from 1 mg to 2 mg for catheter occlusions are both efficacious and safe with minimal ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S155288550570252X

The Use of Alteplase for Treatment of Occluded Central ... Results. Instillation of alteplase was successful in clearing catheter thrombotic occlusions in 66.7% of patients studied in this outpatient population without ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2001/altegen090401lb.pdf

Alteplase (CathFlo Activase), Genentech, Package Insert Trial 1 tested the efficacy of a 2 mg/2 mL Alteplase dose in restoring. 62 function to occluded catheters in 150 patients with catheter occlusion up to. 63. 24 ...

6. cathflo.com cathflo.com/safety.html

Safety Profile - Cathflo® Activase® (alteplase) Read about the Cathflo® Activase® (alteplase) safety profile including indications, contraindications, adverse reactions, and precautions.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK499977/

Alteplase - StatPearls - NCBI Bookshelf - NIH Catheter Clearance. Alteplase 2 mg should be instilled into the catheter at a concentration of 1 mg/mL. A second dose may be administered 2 hours after the ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2002.20.1.317

Safety and Efficacy of Alteplase for Restoring Function in ... PURPOSE: To evaluate the safety and efficacy of alteplase (TPA) for restoring function to occluded central venous catheters (CVCs).

9. cathflo.com cathflo.com/index.html

Cathflo® Activase® (alteplase): Single-Use Vial Lytic ... Excessive pressure should be avoided when Cathflo Activase is instilled into the catheter. Such force could cause rupture of the catheter or expulsion of the ...