Chronic kidney disease (Stages 1-4) Urological and Genital Diseases Chronic kidney disease (Stages 1-4) (CKD)
Conditions
Interventions
Current interventions as of 11/01/2021:
Eligible participants, based on prior results of blood and urine tests, will be randomised (open label randomisation) 1:1 to general practitioner (GP) prescri
Sponsors
University of Southampton
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 20/03/2024: 1. Males and females aged 18 years and over at the date of screening 2. Subjects with CKD (reduced eGFR and/or albuminuria) defined as: 2.1. Estimated glomerular filtration rate [eGFR] <60mL/min/1.73m2 for at least 90 days, and/or 2.2. Kidney disease code on the GP electronic patient AND most recent eGFR in CKD-defining range (<60mL/min/1.73m2), and/or 2.3. Albuminuria or proteinuria (defined as urine albumin:creatinine ratio [ACR] =3mg/mmol, and/or urine protein:creatinine ratio [PCR] =15mg/mmol, and/or +protein or greater on reagent strip) 3. Subjects who are willing to give permission for their paper and electronic medical records to be accessed by trial investigators 4. Subjects who are willing to be contacted and interviewed by trial investigators 5. Subjects who can communicate well with the investigator or designee, understand the requirements of the study and understand and sign the written informed consent _____ Previous inclusion criteria as of 11/01/2021: 1. Aged 18 years or over at the date of screening 2. Subjects with CKD, defined by at least one of the following: 2.1. Decreased estimated glomerular filtration rate [eGFR] for at least 90 days (defined as eGFR <60mL/min/1.73m2), and/or 2.2. Albuminuria or (where there are no measurements of albuminuria) proteinuria for at least 90 days (defined as urine albumin:creatinine ratio [ACR] =3mg/mmol, and/or urine protein: creatinine ratio [PCR] =15mg/mmol , and/or +protein or greater on reagent strip [and in all cases where the most recent qualifying result is ACR =3mg/mmol or PCR =15mg/mmol]), and/or 2.3. CKD formally diagnosed/coded on the GP electronic patient AND most recent quantitative tests within last 15 months and in CKD-defining range (eGFR <60mL/min/1.73m2 and/or ACR =3mg/mmol, and/or PCR =15mg/mmol) 3. Willing to give permission for their paper and electronic medical records to be accessed and abstracted by trial investigators for the duration of the trial 4. Willing to be contacted and interviewed by trial investigators should the need arise for adverse event assessment 5. Able to communicate well with the investigator or designee, to understand and comply with the requirements of the study and to understand and sign the written informed consent _____ Previous participant inclusion criteria as of 08/01/2021: 1. Aged 18 years or over at the date of screening 2. Diagnosed with CKD, defined by at least one of the following: 2.1. Decreased estimated glomerular filtration rate (eGFR) for at least 90 days (defined as eGFR <60 ml/min/1.73m²) 2.2. Albuminuria or, where there are no measurements of albuminuria, proteinuria for at least 90 days (defined as the most recent qualifying result is ACR =3 mg/mmol or PCR =15 mg/mmol, and at least one of the following: urine albumin:creatinine ratio [ACR] =3 mg/mmol, and/or urine protein:creatinine ratio [PCR] =15 mg/mmol, and/or + protein or greater on reagent strip) 2.3. CKD formally diagnosed/coded on the GP electronic patient and most recent quantitative tests within the last 15 months in CKD-defining range (eGFR <60 ml/min/1.73m² and/or ACR =3 mg/mmol, and/or PCR =15 mg/mmol) 3. Willing to give permission for their paper and electronic medical records to be accessed and abstracted by trial investigators for the duration of the trial 4. Willing to be contacted and interviewed by trial investigators should the need arise for adverse event assessment 5. Able to communicate well w
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 20/03/2024: 1. CKD GFR category 5 2. Pre-existing CVD: 2.1. Angina 2.2. Myocardial infarction 2.3. Stroke (ischaemic and haemorrhagic (intracerebral/subarachnoid)) 2.4. Transient ischemic attack 2.5. Significant peripheral vascular disease 2.6. Coronary or peripheral revascularisation for atherosclerotic disease 3. Pre-existing condition associated with increased risk of bleeding other than CKD: 4. Subjects currently prescribed anticoagulants or antiplatelet agent, or taking over the counter (OTC) aspirin continuously 5. Currently and regularly taking other drugs with a potentially serious interaction with aspirin 6. Known allergy to aspirin or definite previous clinically important adverse reaction to aspirin 7. Poorly controlled hypertension (latest recorded systolic blood pressure =180 mmHg and/or diastolic blood pressure =105 mmHg) 8. Subjects with other conditions which in the opinion of their General Practitioner (GP) would preclude prescription of aspirin in routine clinical practice such as significant anaemia or thrombocytopenia 9. Pregnant or likely to become pregnant during the study period 10. Malignancy that is life-threatening or likely to limit prognosis, other life-threatening co-morbidity, or terminal illness 11. Behaviour or lifestyle would render them less likely to comply with study medication 13. In prison 14. Currently participating in another interventional clinical trial or who have taken part in a trial in the last 3 months _____ Previous participant exclusion criteria as of 08/01/2021: 1. CKD GFR category 5 2. Pre-existing CVD: 2.1. Angina 2.2. Myocardial infarction 2.3. Stroke (ischaemic and haemorrhagic (intracerebral/subarachnoid)) 2.4. Transient ischemic attack 2.5. Significant peripheral vascular disease 2.6. Coronary or peripheral revascularisation for atherosclerotic disease Aortic aneurysm is not an exclusion criterion 3. Pre-existing condition associated with increased risk of bleeding other than CKD: 3.1. Upper GI bleed or peptic ulcer in the previous 5 years 3.2. Lower GI bleed in previous 12 months 3.3. Active chronic liver disease (such as cirrhosis) 3.4. Bleeding diathesis (investigator opinion) 4. Taking over the counter aspirin continuously 5. Currently prescribed anticoagulant or antiplatelet agents, including: 5.1. Acenocoumarol, phenindione, warfarin 5.2. Pixaban, edoxaban, rivaroxaban 5.3. Argatroban, bivalirudin, dabigatran 5.4. Aspirin, cangrelor, selexipag, cilostazol, clopidogrel, dipyridamole, prasugrel, ticagrelor, abciximab, eptifibatide, tirofiban, epoprostenol, iloprost 5.5. Unfractionated heparin, dalteparin, enoxaparin, tinzaparin 5.6. Danaparoid, fondaparinux 6. Currently and regularly taking other drugs with a potentially serious interaction with low-dose aspirin, including: 6.1. Non-steroidal anti-inflammatories (except topical preparations), including aceclofenac, acemetacin, celecoxib, dexibuprofen, dexketoprofen, diclofenac (and combination diclofenac-misoprostol preparation), etodolac, etoricoxib, felbinac, fenoprofen, flurbiprofen, ibuprofen, indometacin, ketoprofen, ketorolac trometamol, mefenamic acid, meloxicam, nabumetone, naproxen (and naproxen-esomeprazol), parecoxib, phenylbutazone, piroxicam, sulindac, tenoxicam, tiaprofenic acid, tolfenamic acid 6.2. Selective serotonin re-uptake inhibitors:citalopram, dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline 6.3. Serotonin and noradrenaline re-uptake inhibi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 12/05/2021: Time to first major vascular event from the date of randomisation. A major vascular event is defined as a primary composite outcome of non-fatal myocardial infarction, non-fatal stroke and cardiovascular deathdeath (excluding confirmed intracranial haemorrhage and other fatal cardiovascular haemorrhage). Previous primary outcome measure: Time to first major vascular event from the date of randomisation. A major vascular event is defined as a primary composite outcome of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death (excluding confirmed intracranial haemorrhage). Deaths from other causes (including fatal bleeding) will be treated as competing events. Patients who do not experience a major vascular event will be censored at the date of last follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 12/05/2021: Secondary and tertiary outcome measures will be ascertained from four data sources (unless otherwise stated): 1. Office for National Statistics for mortality and cancer registration 2. Hospital Episode Statistics for hospital admissions 3. General practice Electronic Patient Record for coded cardiovascular episodes, bleeding episodes, coded diagnoses of dementia, recorded eGFR, and prescription of aspirin and other relevant medications 4. Self-reported information (including that from an annual patient questionnaire) The four sources of data will be cross-referenced in order to build up a potential event record. Potential cardiovascular and major bleeding events will be formally adjudicated by an Endpoint Adjudication Committee. The secondary outcome measures are the time to the following events from the baseline (except 1.4): 1. Efficacy: 1.1. Death from any cause 1.2. Composite outcome of major vascular event or revascularisation (coronary and non-coronary) 1.3. Individual components of the primary composite endpoint 1.4. Health-related quality of life, assessed using the EQ-5D-5L at the baseline and annually thereafter 2. Safety: 2.1. Composite outcome of intracranial haemorrhage (fatal and non-fatal), fatal extracranial haemorrhage and non-fatal major extracranial haemorrhage (adjudicated) 2.2. Fatal and non-fatal (reported individually and as a composite) intracranial haemorrhage comprising: 2.2.1. Primary haemorrhagic stroke (to distinguish from haemorrhagic transformation of ischaemic stroke) 2.2.2. Other intracranial haemorrhage (adjudicated). Intracranial haemorrhage will be sub-categorised as traumatic or non-traumatic. 2.3. Fatal and non-fatal (reported individually and as a composite) major extracranial haemorrhage: 2.3.1. Upper gastrointestinal 2.3.2. Lower gastrointestinal 2.3.3. Sight-threatening ocular 2.3.4. Multiple trauma 2.3.5. Other (adjudicated) 2.4. Clinically relevant non-major bleedin | — |
Countries
England, United Kingdom
Contacts
Public Contact. ATTACK study team
Outcome results
None listed