Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial

  title={Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial},
  author={Donald Everett Wesson and Vandana S. Mathur and Navdeep Tangri and Yuri Stasiv and Dawn M Parsell and Elizabeth Li and Gerrit San Jose Klaerner and David A. Bushinsky},
  journal={The Lancet},
Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial
Veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned.
Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis (BiCARB): a pragmatic randomised, double-blind, placebo-controlled trial
  • Miles D. Margaret Aimun Michael K. Gowrie Kolitha Deepak Witham Band Ahmed Almond Balasubramaniam Basnayake, M. Witham, A. Avenell
  • Medicine
    BMC Medicine
  • 2020
Oral sodium bicarbonate did not improve physical function or renal function, increased adverse events and is unlikely to be cost-effective for use by the UK NHS for this patient group.
Efficacy and Safety of Veverimer in the Treatment of Metabolic Acidosis Caused by Chronic Kidney Disease: A Meta-analysis
Current clinical evidence indicates that veverimer is efficacious and safe against metabolic acidosis related to CKD compared with placebo, and further research comparing long-term veVerimer use with traditional alkali therapy is needed.
Effects of Veverimer in Older Adults With CKD and Metabolic Acidosis
Advances in management of chronic metabolic acidosis in chronic kidney disease.
Recent studies suggest that sodium bicarbonate therapy may improve vascular endothelial function and muscle mass, and preserve renal function, and could be a potential new therapeutic option for treating chronic metabolic acidosis.
Mechanism of Action of Veverimer: A Novel, Orally Administered, Nonabsorbed, Counterion-Free, Hydrochloric Acid Binder under Development for the Treatment of Metabolic Acidosis in Chronic Kidney Disease
Veverimer binds and removes hydrochloric acid from the gastrointestinal tract, resulting in increased serum bicarbonate and the correction of metabolic acidosis, and is appropriate for patients with CKD with and without sodium-sensitive comorbidities.
Hyperkalemia in Chronic Kidney Disease in the New Era of Kidney Protection Therapies
K+ pathophysiology and the clinical impact and management of hyperkalemia is reviewed considering these developments and the availability of the novel K+ binders patiromer and sodium zirconium cyclosilicate, recent results from clinical trials targeting metabolic acidosis, and an increasing understanding of the role of the gut microbiota in health and disease.
Effect of Bicarbonate on Net Acid Excretion, Blood Pressure, and Metabolism in Patients With and Without CKD: The Acid Base Compensation in CKD Study.
Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis.


Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD.
TRC101 safely and significantly increased the level of serum bicarbonate in patients with metabolic acidosis and CKD and discontinuation of TRC101 decreased nearly to baseline levels within 2 weeks.
Tolerance to Sodium in Patients With CKD-Induced Metabolic Acidosis: Does the Accompanying Anion Matter?
  • D. Bushinsky
  • Medicine, Biology
    American journal of kidney diseases : the official journal of the National Kidney Foundation
  • 2019
Unless patients with CKD can tolerate a diet virtually devoid of NaCl, additional sodium, regardless of the accompanying anion, appears to increase BP and sodium retention.
Effects of oral sodium bicarbonate in patients with CKD.
NahCO3 supplementation produces a dose-dependent increase in serum bicarbonate and improves lower extremity muscle strength after a short-term intervention in CKD patients with mild acidosis.
Adverse Effects of the Metabolic Acidosis of Chronic Kidney Disease.
Administration of base decreases muscle wasting, improves bone disease, restores responsiveness to insulin, slows progression of CKD, and possibly reduces mortality, and the target serum [HCO3-] remains unclear.
Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR.
It appears that sodium citrate is an effective kidney-protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition in patients with hypertensive nephropathy and metabolic acidosis.
Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism.
Combining results from 4 clinical trials, randomization to cinacalcet led to significant reductions in the risk of parathyroidectomy, fracture, and cardiovascular hospitalization, along with improvements in self-reported physical function and diminished pain.
Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate.
Dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR.
Does correction of metabolic acidosis slow chronic kidney disease progression?
Recent studies suggest that metabolic acidosis mediates nephropathy progression, and its treatment with the comparatively inexpensive and well tolerated intervention of dietary acid reduction holds promise to be an additional kidney-protective strategy in CKD management.
NaHCO3 and NaC1 tolerance in chronic renal failure.
It has been proposed that the NaHCO3 required will not result in clinically significant Na retention comparable to that from similar increases in NaC1 intake and Mechanisms for the greater excretion of Na on NaH CO3 may relate to C1 wasting as noted above on low C1 Intake and limited HCO3 reabsorptive capacity.
Urine Ammonium Predicts Clinical Outcomes in Hypertensive Kidney Disease.
Low ammonium excretion is associated with death and renal failure in hypertensive kidney disease, even among those without acidosis, and could identify patients with CKD and normal bicarbonate levels who might benefit from alkali before acidosis develops.