NCT05786469

Patiromer Trial in CKD Stage IIIB to V

A Prospective, Double-blind, Randomized, Single Centre Trial to Evaluate the Rate of RAAS Inhibitor Withdrawal or Down-titration in Non-dialysis Patients with CKD Stage IIIb to V Randomized to Patiromer or Placebo (DROP)

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Mario Negri Institute for Pharmacological Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase III, prospective, randomized, double-blind, placebo-controlled trial will primarily aim to compare the effects of patiromer and placebo on the rate of withdrawal or down-titration of RAAS inhibition therapy because of refractory hyperkalemia (serum K+ levels ≥ 5.5 mEq/L at two consecutive visits, one-week apart) in non-dialysis patients with CKD stage IIIB to V receiving best available conservative therapy, including RAAS inhibition with ACE inhibitors and/or ARBs and/or aldosterone antagonists. Patients are expected to be included during an 18-month recruitment period. All randomized patients will be maintained on active follow-up for 12 months. At 12 months, a final visit will be performed for all patients who complete the follow-up period. During this final visit, all the parameters evaluated at baseline will be reassessed and the study treatment will be discontinued. Whenever feasible, a final visit will be planned within one month also for those patients who prematurely discontinue the treatment period for any intercurrent reason (adverse event, consent withdrawal and other). After the final visit the patient will be discharged from the study and will be referred to his nephrologist with the suggestion to check serum potassium levels within three days.

Detailed description

Refractory hyperkalemia is among the leading causes of initiation or chronic renal replacement therapy (RRT) by extracorporeal or peritoneal dialysis in patients with chronic kidney disease (CKD). Dialysis therapy is lifesaving but has a major impact on patients' quality of life and is terribly expensive. Thus, deferring dialysis initiation by preventing hyperkalemia would have major implications for patients and health care providers. Among patients with CKD, glomerular filtration rate (GFR) \<45 ml/min/1.73 m2, older age, coexistence of diabetes or heart failure, and inhibition of the renin angiotensin aldosterone system (RAAS) by angiotensin-converting-enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) or aldosterone antagonists are the major risk factors for hyperkalemia. On the other hand, RAAS inhibitors - based on randomized trial results showing the superior effect of these medications compared to other antihypertensive drug classes in slowing the progression of chronic nephropathies to end-stage renal disease (ESRD) - are first-line therapy for patients with CKD, in particular for those with proteinuric nephropathies. However, the risk of hyperkalemia is a major impediment to adequate RAAS blockade in CKD, especially when RAAS inhibitors are used in maximal doses or are combined. Dietary counseling, correction of metabolic acidosis and treatment with loop diuretics are key components of potassium-lowering therapy in patients with CKD. Combined therapy with potassium binders, however, is often needed to prevent or treat hyperkalemia, particularly in patients with GFR \<45 ml/min/1.73 m2, concomitant diabetes and/or RAAS inhibitor therapy. A newer potassium binder, patiromer, has been approved by FDA and EMA for the treatment of hyperkalemia. Patiromer is an organic, non-absorbed, sodium-free, potassium-binding polymer that exchanges potassium for calcium in the gastrointestinal tract. Because of the remarkably good risk/benefit profile, it is conceivable that patiromer may safely improve hyperkalemia control and reduce the need of RAAS inhibition interruption or down-titration (not only of ACE inhibitors and ARBs but also of potassium sparing diuretics such as spironolactone, eplerenone and finerenone) in patients with severe CKD. In turn, this could translate into improved nephroprotection and deferred initiation of dialysis, particularly in non-dialysis patients with CKD stage IV to V. This hypothesis, however, must be tested in prospective randomized controlled trials.

Conditions

• Hyperkalemia

Interventions

Type	Name	Description
DRUG	Veltassa Oral Powder Product	The recommended starting dose is 8.4 g of patiromer, once daily (equivalent to one packet of the active ingredient, once daily). The daily dose may be adjusted in intervals of one week or longer, based on the serum potassium level and the desired target range. The daily dose may be increased or decreased by 8.4 g as necessary to reach the desired target range, up to a maximum dose of 25.2 g daily. If serum potassium falls below the desired range, the dose should be reduced or discontinued. Patients are expected to be included during an 18-month recruitment period. The last randomized patient will be maintained on active follow-up for 6 months. All other randomized patients will be maintained on active follow-up until the last randomized patient will have completed the planned 6-month follow-up period. Thus, the follow-up period will be expected to range from a minimum of 6 months for the last randomized patient to a maximum of 24 months for the first randomized patient
OTHER	Placebo	The recommended starting dose is 8.4 g of patiromer, once daily (equivalent to one packet of the active ingredient, once daily). The daily dose may be adjusted in intervals of one week or longer, based on the serum potassium level and the desired target range. The daily dose may be increased or decreased by 8.4 g as necessary to reach the desired target range, up to a maximum dose of 25.2 g daily. If serum potassium falls below the desired range, the dose should be reduced or discontinued. Patients are expected to be included during an 18-month recruitment period. The last randomized patient will be maintained on active follow-up for 6 months. All other randomized patients will be maintained on active follow-up until the last randomized patient will have completed the planned 6-month follow-up period. Thus, the follow-up period will be expected to range from a minimum of 6 months for the last randomized patient to a maximum of 24 months for the first randomized patient

Timeline

• Start date: 2023-08-02
• Primary completion: 2024-11-07
• Completion: 2024-11-07
• First posted: 2023-03-27
• Last updated: 2024-11-12

Locations

1 site across 1 country: Italy