Study on the Thrombolytic Effect of Platelet Membrane Coated Recombinant Staphylokinase on Human Arterial Thrombus

Arterial Thrombosis Clinical Trial

Official title:

Study on the Thrombolytic Effect of Platelet Membrane Coated Recombinant Staphylokinase on Human Arterial Thrombus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05978791
• Other study ID #: 021
• Status: Recruiting
• Start date: October 11, 2023
• Est. completion date: June 2024

Study information

• Verified date: October 2023
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Chunjian Li, PhD
• Phone: +86 13701465229
• Email: lijay[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology in 1985, which has better thrombolytic effect than streptokinase (SK) and urokinase (UK). It has similar biological properties to natural SAK, is highly selective to fibrin, does not activate systemic fibrinolysis, and can dissolve clots in a short period of time without significantly increasing the risk of bleeding, especially for platelet-rich arterial clots. Previous studies have shown that the thrombolytic revascularization rate of r-SAK is significantly better than that of r-SK and UK at the same dose in the rabbit model of acute femoral artery occlusive thrombosis. The revascularization rate of coronary artery at 90 minutes after thrombolysis was significantly higher with r-SAK than r-tPA. The combination of thrombolytic drugs and nanocarriers may provide a new solution for the existing thrombolytic therapy. Inspired by the natural affinity of platelets (PLT) in hemostasis and pathological thrombosis, we have developed a thrombus targeting nanocarrier, which is a platelet membrane cloaked r-SAK（PLT-SAK）and compare the thrombolytic effect of PLT-SAK with different doses of free r-SAK on human arterial thrombus, aiming to further improve the thrombolytic effectiveness of r-SAK.

Description:

Currently, the most important treatment for thrombus and related cardiovascular diseases is prevention, but in the case of long-term thrombosis, the main treatment options include balloon catheters, surgical removal of embolus, thrombolytic therapy, and other related operations. Considering the cost of surgical treatment and its damage to the body, thrombolytic therapy has become one of the most effective ways to achieve rapid thrombus clearance and recanalization of blocked blood vessels in thrombotic diseases. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology in 1985, which has better thrombolytic effect than streptokinase (SK) and urokinase (UK). It has similar biological properties to natural SAK, is highly selective to fibrin, does not activate systemic fibrinolysis, and can dissolve clots in a short period of time without significantly increasing the risk of bleeding, especially for platelet-rich arterial clots. Previous studies have shown that the thrombolytic revascularization rate of r-SAK is significantly better than that of r-SK and UK at the same dose in the rabbit model of acute femoral artery occlusive thrombosis. The revascularization rate of coronary artery at 90 minutes after thrombolysis was significantly higher with r-SAK than r-tPA. The combination of thrombolytic drugs and nanocarriers may provide a new solution for the existing thrombolytic therapy. Inspired by the natural affinity of platelets (PLT) in hemostasis and pathological thrombosis, we have developed a thrombus targeting nanocarrier, which is a platelet membrane cloaked r-SAK（PLT-SAK）and compare the thrombolytic effect of PLT-SAK with different doses of free r-SAK on human arterial thrombus, aiming to further improve the thrombolytic effectiveness of r-SAK.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

For CAD patients:

Inclusion Criteria:

1. Age 18-75 years old, body weight =45kg, regardless of gender;

2. Patients with suspected coronary artery disease scheduled for coronary angiography or interventional therapy.

3. Take aspirin and ticagrelor maintenance dose =3 days, or loading dose of aspirin (300mg) and ticagrelor (180mg) =12 hours;

Exclusion Criteria:

1. Previous thrombolytic therapy with r-SAK;

2. A previous diagnosis of Staphylococcus aureus infection;

3. Those who are enrolled in other clinical trials;

4. Those who were deemed ineligible by other investigators. For healthy volunteer:

Inclusion Criteria:

1. Age 18-75 years old, body weight =45kg, regardless of gender;

Exclusion Criteria:

1. Currently taking any medication that may affect platelet function, such as antiplatelet drugs or nonsteroidal anti-inflammatory drugs.

2. Individuals with blood disorders, active bleeding or a tendency to bleed, including platelet count <100×10^9/L, hemoglobin <100g/L, or recent bleeding in the digestive system or urinary tract within one month.

3. Individuals with impaired liver or kidney function, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels above the upper limit of normal reference range, and estimated glomerular filtration rate (eGFR) <90 mL/min/1.73m^2 (calculated based on the CKD-EPI equation).

4. Recent (within one month) severe trauma, surgery, or head injury.

5. Pregnant or lactating women.

6. Diabetes.

7. Smokers.

8. Those who are enrolled in other clinical trials;

9. Those who were deemed ineligible by other investigators.

Related Conditions & MeSH terms

• Arterial Thrombosis
• Thrombosis

Intervention

Procedure:
• collection of venous blood or arterial blood
Partial CAD patients were collected 20 mL arterial blood samples 12 hours after the last intake of 100mg aspirin and 2 hours after intake of 90mg ticagrelor. The blood samples were divided into 2 mL centrifuge tubes, with each containing 1.0 mL (for preparation of blood clots). Partial CAD patients were collected 40 mL blood samples into sodium citrate anticoagulant tubes 12 hours after the last intake of 100mg aspirin and 2 hours after intake of 90mg ticagrelor (for preparation of platelet-poor plasma, PPP). Healthy volunteer (group 1) collected 40 mL blood samples into sodium citrate anticoagulant tubes (for preparation of PPP). Healthy volunteer (group 2) collected 9 mL venous blood samples (for platelet aggregation assay).

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (25)

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombolysis rate	Thrombolysis rate (%) = [(initial clot weight - final clot weight) / initial clot weight] × 100%.	60 min
Secondary	Adenosine diphosphate-induced platelet aggregation rate.	9 mL venous blood was collected from healthy volunteers (group 2) into 3.2% sodium citrate tubes and subjected to platelet aggregation assay by light transmission aggregometry within 120min.Also test the effect of 20% aspirin- and ticagrelor-treated PPP and 20% healthy volunteers (group 1) PPP on platelet aggregation.	120 min