We plan a large pragmatic trial to test the potential for spironolactone to to reduce overall cardiovascular events and death, to delay the decline in renal function, and to improve surrogate markers for vascular disease in people with stage 3b (eGFR 30-44 ml/min/1.73m2)Chronic Kidney Disease. MedDRA version: 15.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857 MedDRA version: 15.1 Level: PT Classification code 10018355 Term: Glomerular fil
Conditions
Interventions
Trade Name: Spironolactone (Non-proprietary)
Product Name: Spironolactone
Product Code: 0025-1001
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: spironolactone
CAS Number: 52-01-7
Concen
Sponsors
University of Oxford, Clinical Trials and Research Governance Office
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Participant is willing and able to give informed consent for participation in the study. • Male or Female, aged 18 years or above. • Evidence of stage 3b CKD using the MDRD equation. This includes patients on the CKD register undergoing annual monitoring who have had 2 or more recent samples in the 3b range. as well as patients with at least two consecutive blood samples within the preceding 12 months (with a minimum of 6 weeks between tests) and no identifiable reason for a temporary reduction in eGFR. Where only one test has been performed and is in the 3b range, GPs will be reminded that standard care suggests a second confirmatory test. • Able (in the recruiting GP’s opinion) and willing to comply with all study requirements. • Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study. • Willing to provide contact details to the Research Team, for use at any time should the need arise, on trial related matters. • If the participant is a female of child-bearing potential, they are willing to ensure effective contraception during the trial period. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 616 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2000
Exclusion criteria
Exclusion criteria: • Female participants who is pregnant, lactating or planning pregnancy during the course of the study. • Type 1 diabetes mellitus • Terminal disease or felt otherwise unsuitable by their GP. • Chronic heart failure clinical diagnosis or known LVSD with EF 70 mg/mmol. • Prescription of medications with known harmful interactions with spironolactone as documented in the British National Formulary including tacrolimus, lithium and cyclosporine. • Any other significant disease or disorder which, in the opinion of the recruiting GP, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of aldosterone receptor antagonism on mortality and cardiovascular outcomes (onset or progression of cardiovascular disease) in patients with stage 3b CKD.;Secondary Objective: To determine the effect of aldosterone receptor antagonism in patients with stage 3b CKD on: 1. Measures of cardiovascular haemodynamics 2. Left ventricular function 3. Decline in renal function 4. Treatment costs and benefits 5. Incidence of TIA 6. To determine the safety of ARA in patients with stage 3b CKD ;Primary end point(s): Composite of death or first onset or hospitalisation for heart disease (coronary heart disease, arrhythmia, new onset/first recorded atrial fibrillation, sudden death, failed sudden death), stroke, or heart failure at 3 years. Primary end-points will be adjudicated by an independent end-points committee blinded to treatment arm.;Timepoint(s) of evaluation of this end point: An evaluation of whether the primary outcome has been met will be performed at each trial visit by the member of the research team performing that visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in carotid-femoral pulse wave velocity from baseline to final visit – intensively phenotyped group. • Change in blood pressure at final visit and annually • Rates of hypotension (20 mmHg systolic drop on standing) • Mean change in ambulatory blood pressure from randomisation to final visit (measured in mmHg) – intensively phenotyped group. • Changes in BNP. • Change in ACR • Changes in eGFR • Change in health status on EQ-5D-5L • Cost effectiveness analysis • Transient Ischaemic Attack – as defined by the American Heart Association (2009) • Rates of adverse events o Rates of hyperkalaemia ;Timepoint(s) of evaluation of this end point: Due to the nature of the analysis of the secondary endpoints, which requires all results to have been collected, the evaluation will take place once all visits are complete. | — |
Countries
United Kingdom
Contacts
Public ContactBen Thompson
Department of Primary Care Health Sciences, University of Oxford
Outcome results
None listed