Inhibiting white blood cell function as a new way to treat coronary heart disease

Phase 2

• Conditions: Coronary heart disease; Circulatory System

• Registration Number: ISRCTN48328178
• Lead Sponsor: King's College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-02-25
• Study Completion: 2022-02-28
• Last Update Posted: 27 March 2023

Recruitment & Eligibility

• Status: Stopped
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

1. Men and women = 18 years of age
2. Angiographically proven coronary heart disease undergoing native-vessel PCI for non-ST-elevation myocardial infarction or unstable or stable coronary disease
3. Absolute blood neutrophil count at the time of PCI as well as 4 weeks after PCI of >4.0 x 109/L
4. Otherwise receiving standard of care for ischaemic heart disease (including appropriate anti-platelet therapy, statin, antihypertensive as clinically indicated)

Exclusion Criteria

1. At any time after initial screening (ie at the time of PCI + IVUS), requirement or anticipated requirement, by clinical care guideline or in the opinion of the treating physician, for a new medication which may affect trial primary and / or secondary endpoints (ie specifically new lipid lowering therapy, anti-hypertensive therapy, or immunomodulatory therapy). Note that dose titration of chronic therapy initiated prior to PCI is permissible during the trial.
2. History of inability or, in the opinion of the investigator, anticipated inability to tolerate adenosine-based pharmacologic stress testing (e.g. active pulmonary broncho-constrictive disorder, second or third degree AV block without a cardiac pacemaker, resting systolic blood pressure <90mmHg, unstable coronary disease, use of medications which may interfere with the test)
3. Acute ST-elevation myocardial infarction
4. Prior cardiovascular surgery
5. Significant vascular anatomic abnormality which in the opinion of the investigator portends unacceptable risk to serial coronary IVUS examination
6. Scheduled inpatient surgery or planned hospitalisation during the study period
7. Any clinically significant disease or disorder (eg, cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, psychiatric, major physical impairment) which, as judged by the investigator, might put the patient at risk because of participation in the study
8. Recurrent, latent, or chronic infections, as judged by the investigator, or with a history of osteomyelitis, or at risk of infection (surgery, trauma, or significant infection within 30 days before enrolment), or with a history of skin abscesses or a soft tissue infection within 60 days before enrolment
9. Evidence of active tuberculosis, either treated or untreated, or latent tuberculosis without completion of an appropriate course of treatment or appropriate ongoing prophylactic treatment
10. Positive test for serum hepatitis B surface antigen, hepatitis C antibody, or HIV
11. Patients vaccinated with a live or live-attenuated vaccine in the 2 weeks prior to enrolment
12. Use of any immunosuppressive treatment (eg, methotrexate, troleandomycin oral gold, cyclosporine, azathioprine, intramuscular long-acting corticosteroid [except for asthma exacerbations]) within 60 days prior to enrolment
13. Prior solid organ or bone marrow transplantation
14. History of any primary immunodeficiency disorder excluding asymptomatic selective IgA or IgG subclass deficiency
15. Active malignancy or neoplastic disease in the previous 5 years other than superficial basal cell carcinoma
16. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level =2.5 times the upper limit of normal (ULN) 4 weeks after PCI
17. QTc of >450 ms for males and 470 ms for females 4-weeks after PCI
18. Current evidence of drug abuse or significant history of drug abuse, as judged by the investigator.;
19. Current evidence of alcohol abuse or a significant history of alcohol abuse, as judged by the investigator
20. Pregnancy or breast feeding during the study
21. Contraindication to any of the study tre

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Coronary vascular function, measured by change in coronary flow reserve (a measure of the coronary arteries to dilate, assessed by PET scanning, and, in a subset, invasive coronary flow measurements) from baseline to 6 months.

Secondary Outcome Measures

Name	Time	Method
<br> 1. Change in plaque composition, measured using intravascular ultrasound (IVUS) at baseline and at 24 weeks<br> 2. Degree of in-stent restenosis, measured using intravascular ultrasound at baseline and at 24 weeks<br> 3. Change in microvascular resistance, done by by CombiWire assessment (involving insertion of a specialised flow-measurement wire into the coronary arteries) at baseline and at 6 months (on a subgroup of patients)<br>