Clarifying Optimal Sodium InTake In Cardiovasular and Kidney (COSTICK) Diseases: a study protocol for two randomised controlled trials.

Background: While low sodium intake (<2.3g/day) is recommended for all, there is uncertainty about feasibility and net cardiovascular effects. In COSTICK, we evaluated the effects of a dietary counselling intervention (reduced sodium intake) on intermediate cardiorenal outcomes in patients with (STICK) and without (COSIP) mild/moderate kidney disease. Methods: This is a protocol for two phase IIb randomised, two-group, parallel, open-label, controlled, single centre trials. Participants were aged >40 years with stable blood pressure, unchanged anti-hypertensive medications, willing to modify diet and provided written informed consent. Participants were excluded for abnormal sodium handling, heart failure, high dose diuretics, immunosuppression, pregnancy/lactation, postural hypotension, cognitive impairment, high or low body mass index (BMI) or inclusion in another trial. STICK participants had estimated glomerular filtration rate (eGFR) 30-60ml/min/1.73m 2 and were excluded for acute kidney Injury, rapidly declining eGFR; known glomerular disease or current use of non-steroidal anti-inflammatory drugs. For COSIP, participants were excluded for known kidney or cardiovascular disease. Participants were randomized to usual care only (healthy eating) or an additional sodium lowering intervention (target <100mmol/day) through specific counseling (sodium use in foods, fresh over processed foods, sodium content of foods and eating outside of home). In STICK the primary outcome is change in 24-hour urinary creatinine clearance. In COSIP, the primary outcome is change in five biomarkers (renin, aldosterone, high sensitivity troponin T, pro-B-type natriuretic peptide and C-reactive protein). Our primary report (COSTICK), reports six biomarker outcome measures in the entire population at 2 years follow-up. Discussion: These Phase II trials will explore uncertainty about low sodium intake and cardiovascular and kidney biomarkers, and help determine the feasibility of low sodium intake. Trial results will also provide preliminary information to guide a future definitive clinical trial, if indicated. Trial registration: STICK: ClinicalTrials.gov NCT02738736 (04/04/2016); COSIP: ClinicalTrials.gov NCT02458248 (15/05/2016).