Chronic obstructive pulmonary disease (COPD) Respiratory
Conditions
Interventions
2x2 factorial design trial. Participants will be randomised to of the following:
1. Aspirin 75mg with 1g omega-3 once daily
+placebo colchicine 500mcg every other day (alternate days) for 12 weeks.
2. Colchicine 500mcg every other day
+ placebo aspirin 75mg with placebo 1g omega 3 once daily for 12 weeks.
3. Aspirin 75mg with 1g omega-3 once daily
+colchicine 500mcg every other day for 12 weeks
4. Placebo colchicine 500mcg every other day
+ placebo aspirin 75mg with placebo 1g omega 3 once daily for 12 weeks.
Sealed Envelope Ltd (https://www.sealedenvelope.com/) used for randomisation system.
Sponsors
Cambridge Clinical Trials Unit (CCTU)
Eligibility
Sex/Gender
All
Age
40 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Be willing and able to give consent to participate 2. Individuals with a COPD exacerbation 3. Aged 40 years and older 4. In the Investigator’s opinion, willing and able to comply with trial requirements
Exclusion criteria
Exclusion criteria: 1. Inability to take the trial medication 2. Allergy or unsuitable for trial medications, including hypersensitivity or allergy to any of the trial drugs: aspirin, colchicine, omega-3, salicylic acid compounds, or prostaglandin synthetase inhibitors or excipients (including allergy to peanuts or soya \[lecithin], gelatine, glycerol, fish). Please see Trial Procedures Manual (TPM) for full list of excipients 3. Diagnosis of aspirin/NSAID-induced asthma (diagnosis of asthma itself is not an exclusion criterion) 4. Patients diagnosed with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption, as medicine contains lactose 5. Already taking aspirin and/or colchicine, antiplatelets^, warfarin; concurrent treatment with systemic oral carbonic anhydrase inhibitors (acetazolamide), oral uricosuric drugs (e.g., probenecid, sulfinpyrazone), P-glycoprotein (P-gp) inhibitors or moderate-strong CYP 3A4 inhibitors (macrolides, diltiazem, verapamil, azoles, ritonavir, ciclosporin), methotrexate use (>15 mg/week). 6. Women of childbearing potential (WoCBP)+, unless using effective measures of contraception; pregnancy, planned pregnancy during the trial (52 weeks), breastfeeding 7. Any medical history or clinically relevant abnormality that makes the patient ineligible for inclusion in the trial because of a safety concern relating to participating in the trial or trial medications 8. Progressive neuromuscular disorder, myositis, myopathy, raised CK on statins 9. Participant with life expectancy of less than 3 months 10. Known immunocompromise, defined as a diagnosed immunodeficiency disorder (e.g., HIV-1 or HIV-2) or regular use of systemic immunosuppressive therapy (excluding physiologic replacement doses of hydrocortisone or prednisolone for adrenal insufficiency, which are permitted) 11. Clinically significant renal impairment, including haemodialysis or filtration use, eGFR 150 mmol/L 12. Clinically significant hepatic impairment, including presence of liver cirrhosis, ascites, encephalopathy, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level that is persistently =1.5 times the upper limit of normal 13. Blood dyscrasia (i.e., leukopenia \[WCC <4.0 x10?/L\*], thrombocytopenia \[<110 x10?/L], anaemia \[Hb <110 g/L]). \*Drop in WCC may occur with an intercurrent viral exacerbation. Rescreening of blood results is permitted as values are often variable 14. Patients with current or historical conditions that significantly increase bleeding risk, including active bleeding, prior major haemorrhage (e.g., cerebrovascular or gastrointestinal, gastroduodenal ulcer, gastroduodenal perforation due to ulceration), coagulation disorders (e.g., haemophilia, thrombocytopenia) 15. Current participation in another clinical trial of investigational medicinal product (CTIMP) or intervention 16. Patients whose increased respiratory symptoms are primarily attributable to an alternative diagnosis (e.g., pneumonia, ongoing sepsis, pulmonary embolism, pneumothorax, acute cardiovascular event such as ACS or heart failure) rather than an acute exacerbation of COPD
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incident of treatment failure up to 12 weeks from starting standard of care treatment of COPD: Treatment failure is composite of requirement of re-treatment of a COPD exacerbation (i.e; oral corticosteroids and/or oral antibiotics), hospitalisation from any cause, or death, measured using patient report and/or using data collected from the patient’s medical records at 2, 4 and 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Respiratory symptoms measured using the COPD Assessment Test (CAT), Visual Analogue Scale (VAS), Breathlessness, Cough, and Sputum Scale (BCSS) and the Modified Medical Research Council Dyspnea Scale (mMRC) scoring at baseline, 2, 4 and 12 weeks;Duration from COPD exacerbation onset to participant recovery measured using patient report and/or using data collected from the patient’s medical records at 2, 4 and 12 weeks;Time to treatment failure from starting standard of care treatment of COPD until week 12 measured using patient report and/or using data collected from the patient’s medical records at 2, 4, and 12 weeks;Number, rate and severity of exacerbations and time to next exacerbation during the first 12 weeks measured using patient report and/or using data collected from the patient's medical records on the requirement of additional steroids and/or antibiotics to treat an exacerbation at 2, 4 and 12 weeks;Length of exacerbation-free status in the trial during the first 12 weeks, where there was no requirement for further use of steroids and/or antibiotics to treat an exacerbation, measured using patient report an/or using data collected from the patients' medical records at 2, 4 and 12 weeks;Cardiovascular events measured using patient report and/or using data collected from the patient's medical records at 2, 4 and 12 weeks;Mortality measured using medical records at 2, 4 and 12 weeks;Hospitalisation measured using patient report and/or patient's medical records at baseline, 2, 4 and 12 weeks;Healthcare usage during the first 12 weeks measured using patient report and/or patient's medical records on hospitalisation, GP attendance, urgent care use and emergency service telephone use at baseline, 2, 4 and 12 weeks;Participant reported adherence and tolerability measured using a Likert scale at baseline, 2, 4 and 12 weeks;Adverse events of special interest and serious adverse reactions from baseline up to 12 weeks measured using patient report and/or patient's m | — |
Countries
England, United Kingdom
Contacts
Public Contact- EASE-COPD Central Trial Coordinator
Outcome results
None listed