CLArithromycin for post-Stroke Pneumonia: A prospective, randomised open-label blinded-endpoint (PROBE) phase 3 multicentre trial
Post Stroke Pneumonia
Consented participants will be allocated to either the treatment arm or usual care in a 1:1 ratio via a web-based interface integrated into the electronic Case Report Form (eCRF). • Intervention arm: Clarithromycin 500mg twice daily for 5 days total (route of administration will be determined by the local clinical team based on clinical condition and availability of route of administration in line with local policy) in addition to usual non-macrolide antibiotic treatment. • Usual care: Local stroke unit usual non-macrolide antibiotic treatment. All participants will be followed up at Day 7 (safety, intervention doses administered, other antibiotics administered, vital signs, examination findings, provision of contact details for follow-up) and Day 90 (remote collection of data required for outcomes).
1. Age ≥18 years 2. Acute stroke (ischaemic stroke or intracerebral haemorrhage [ICH]) within the past 14 days 3. Starting (or within 24 hours of starting) non-macrolide antibiotics for a new diagnosis of PSP 4. Written informed consent from participant or from Next of Kin / designated representative or consultee or Independent Physician if lacks capacity (by phone if required) 5. Women of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) or urine test at screening
1. Requirement for macrolide therapy as usual care 2. Confirmed respiratory viral infection (e.g. COVID-19, influenza) at point of screening 3. Known antibiotic treatment for chest infection or pneumonia within the last two weeks (single doses or less than 3 days of treatment is allowed) 4. Known toxin positive C.difficile infection in the past 12 weeks 5. Contraindications or major cautions to macrolide antibiotic use: 5.1. Known hypersensitivity to clarithromycin, its excipients or other macrolide antibiotics 5.2. Established diagnosis of myasthenia gravis 5.3. Diagnosis of long QT syndrome 5.4. QTc interval >460ms on last ECG before screening 5.5. Known uncorrected hypokalaemia (K+ < 3.5 mmol/l) which has not been corrected 5.6. Known uncorrected hypomagnesaemia (Mg2+ < 0.85 mmol/l) which has not been corrected 5.7. History of ventricular tachycardia 5.8. History of cardiac arrest 5.9. Severe hepatic impairment defined as AST, ALT or bilirubin > 3 times ULN or known diagnosis of cirrhosis 5.10. Current use of medicine(s) known to increase risk of QT prolongation that in the opinion of the investigator cannot reasonably be withheld for the duration of study treatment plus 3 days 5.11. Current use of medicine(s) that are contra-indicated in combination with clarithromycin that in the opinion of the investigator cannot reasonably be withheld for the duration of study treatment plus 3 days 6. Women of childbearing potential who are pregnant, breastfeeding or who are unwilling to use appropriate contraception or abstain from sexual intercourse for 3 days (72 hours) after the last dose of clarithromycin 7. Plan for imminent mechanical ventilation 8. End-of-life care 9. Previously randomised into the CLASP study