DIAMOND Study

• Research type

  Research Study

• Full title

  A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal, Parallel Group Study of Patiromer for the Management of Hyperkalemia in Subjects Receiving Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Medications for the Treatment of Heart Failure (DIAMOND)

• IRAS ID

  271539

• Contact name

  John Cleland

• Contact email

  john.cleland@glasgow.ac.uk

• Sponsor organisation

  Relypsa, Inc., a Vifor Company

• Eudract number

  2018-005030-38

• ISRCTN Number

  ISRCTN00000000

• Clinicaltrials.gov Identifier

  NCT03888066

• Clinicaltrials.gov Identifier

  075615, IND Number

• Duration of Study in the UK

  1 years, 9 months, 30 days

• Research summary

  Summary of Research
  A study has commenced on the investigational use of an already approved medication called patiromer, as a possible treatment for the management of high potassium in the blood in patients with heart failure. \n\nRenin-angiotensin-aldosterone system inhibitor (RAASi) medications (commonly used in treating patients with heart failure) are known to cause high potassium in some patients, which can be a dangerous. Patients with kidney problems are especially vulnerable. High potassium would usually cause RAASi treatment to be decreased or stopped, despite the overall known effectiveness of RAASi’s in helping patients live longer and avoid hospitalisations and other cardiovascular events. \n\nThis study will evaluate whether patiromer can manage blood potassium in patients who either already have high potassium or who are at high risk of developing it while receiving RAASi medication. The study will also investigate whether such patients can benefit from RAASi medications in the same way as those without potassium problems to begin with.\n\nThis study will include about 2388 adult participants at approximately 350 research centres globally.\n\nParticipation duration will vary significantly among participants and should be prepared to be in this study for up to 2.5 years or more. \n\nAfter study screening to check eligibility, the study will be divided into 2 time periods: \n\n•\tA Run-in period - of up to 12 weeks, for management of potassium levels and \n•\tA Treatment period - of at least 6 months whereby participants will be assigned to receive study medication.\n\nRegular medical care will continue and the study will continue until the required number of composite endpoint events have occurred.\n\nInformed consent must be obtained from each participant before any study procedures are performed. At scheduled study visits, participants will visit the centre where study assessments will take place e.g. physical exam, vital signs, ECG’s (recording of the heart), blood and urine tests and completion of questionnaires.\n\nSide effects will be monitored throughout the study.\n

  Summary of Results
  A total of 1642 patients with HFrEF and current or a history of renin-angiotensin aldosterone system inhibitor (RAASi) related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimisation of RAASi therapy (≥50% recommended dose of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist [MRA] spironolactone or eplerenone). Specified target doses of RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13, 43) weeks, the adjusted mean change in potassium was +0.03 mmol/L in the patiromer group and +0.13 mmol/L in the placebo group (difference in adjusted mean change between patiromer and placebo: -0.10 [95% confidence interval, CI -0.13, -0.07] mmol/L, P<0.001). Risk of hyperkalemia >5.5 mmol/L (hazard ratio [HR] 0.63; 95% CI 0.45, 0.87; P=0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P=0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P<0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P<0.001) and total RAASi use score (win ratio 1.25, P=0.048) favored the patiromer arm. Adverse events were similar between groups.

• REC name

  Yorkshire & The Humber - Leeds West Research Ethics Committee

• REC reference

  19/YH/0400

• Date of REC Opinion

  7 Jan 2020

• REC opinion

  Further Information Favourable Opinion