Urodilatin (ularitide) / Cardiorentis - LARVOL DELTA

(Pro)renin, Erythropoietin, Vitamin D and Urodilatin Release From Human Donor Kidneys During Normothermic Machine Perfusion: Predictors of Early Post-Transplant Outcome? (PubMed, Clin Transplant) - P2 | "Urodilatin release in urine and EPO and active vitamin D release in perfusate during NMP may serve as potential biomarkers for predicting early post-transplant outcomes."

Biomarker • Journal • CNS Disorders • Transplantation

Randomized clinical trial on safety of the natriuretic peptide ularitide as treatment of refractory cirrhotic ascites. (PubMed, Hepatol Commun) - P2 | "Ularitide in doses of 20-30 ng/kg/min did not benefit urine production and renal sodium excretion rate in patients with refractory ascites. The participants randomized to ularitide overall developed more adverse reactions than placebo. EudraCT no. 2019-002268-28."

Clinical • Journal • Fibrosis • Hepatology • Immunology

Safety and Efficacy of the Natriuretic Peptide Ularitide in Refractory Cirrhotic Ascites: Interim Analysis of a Randomized Controlled Trial (EASL-ILC 2024) - "Ularitide in doses of 30 and 20 ng/kg/min did not show clinically meaningful effects on urine volume and renal sodium excretion rate after 24 hours of continuous intravenous infusion. The participants randomized to ularitide developed significant reductions in blood pressure and had more adverse reactions compared with placebo. Further studies are needed to clarify the optimal dose and treatment regimen of ularitide in patients with refractory ascites."

Clinical • Fibrosis • Hepatology • Immunology • Portal Hypertension

New Pharmacotherapeutic Classes for the Management of Heart Failure: A Narrative Review. (PubMed, Cureus) - "We focus on vericiguat, omecamtiv mecarbil, ularitide, and serelaxin, and thoroughly examine their efficacy and safety profiles while summarizing the clinical trials of the drugs. There is a need for more long-term studies comparing the efficacy of these medications to the conventional ones."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure

Human Transplant Kidneys on Normothermic Machine Perfusion Display Endocrine Activity. (PubMed, Transplant Direct) - "NMP perfusate was collected at 3 time points (0, 1, 2 h) for the measurements of prorenin/renin, erythropoietin (EPO), and vitamin D, and urine samples were collected at 1 h and 2 h for urodilatin measurement...Human transplant kidneys display endocrine activity during NMP. To explore whether correlations exist between hormone release rates and posttransplant kidney function, large numbers of kidneys are required."

Journal • CNS Disorders • Nephrology • Transplantation

The Natriuretic Peptide System: A Single Entity, Pleiotropic Effects. (PubMed, Int J Mol Sci) - "The characterization of their receptors, the understanding of the molecular mechanisms through which they exert their action, and the discovery of new peptides in the last period have made it possible to increasingly feature the physiological and pathophysiological role of the members of this family, also allowing to hypothesize the possible settings for using these molecules for therapeutic purposes. This literature review traces the history of the discovery and characterization of the key players among the natriuretic peptides, the scientific trials performed to ascertain their physiological role, and the applications of this knowledge in the clinical field, leaving a glimpse of new and exciting possibilities for their use in the treatment of diseases."

Journal • Review • Cardiovascular

ULA04: Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide. (clinicaltrials.gov) - P2 | N=17 | Terminated | Sponsor: University of Aarhus | N=38 ➔ 17 | Trial completion date: Aug 2023 ➔ Nov 2022 | Recruiting ➔ Terminated; Interim analysis showing safety concerns

Enrollment change • Trial completion date • Trial termination • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

Efficacy of pharmacologic therapies in patients with acute heart failure: A network meta-analysis. (PubMed, Front Pharmacol) - " After screening 14,888 citations, 23 RCTs (17,097 patients) were included, focusing on nesiritide, placebo, serelaxin, rhANP, omecamtiv mecarbil, tezosentan, KW-3902, conivaptan, tolvaptan, TRV027, chlorothiazide, metolazone, ularitide, relaxin, and rolofylline. No drug was superior to the other drugs for the secondary outcomes and safety outcomes. Current drugs for AHF show similar efficacy and safety."

Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Heart Failure

Effects and safety of natriuretic peptides as treatment of cirrhotic ascites: A systematic review and meta-analysis. (PubMed, World J Hepatol) - "Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites. Continuous infusion rates > 30 ng/kg/min are the most effective. However, safety increases with infusion rates ≤ 30 ng/kg/min."

Journal • Retrospective data • Review • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

ULA04: Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide. (clinicaltrials.gov) - P2 | N=38 | Recruiting | Sponsor: University of Aarhus | Trial primary completion date: Aug 2022 ➔ Jan 2023

Trial primary completion date • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

Ularitide as treatment of refractory ascites in cirrhosis- a study protocol for a randomised trial. (PubMed, Dan Med J) - P2 | "TRIAL REGISTRATION Clinicaltrials.gov (NCT04311489) and EU Drug Regulating Authorities Clinical Trials (EudraCT: 2019-002268-28). The trial will be conducted in accordance with good clinical practice, the Declaration of Helsinki and applicable demands from Danish authorities."

Clinical • Journal • Fibrosis • Hepatology • Immunology

Modified Natriuretic Peptides and their Potential Role in Cancer Treatment. (PubMed, Biomed J) - "The in vitro experiments also show that cardiac hormones, CNP and urodilatin can effectively inhibit the growth of most tumor cells...Peptide therapy is a very promising field for cancer treatments since they can induce the death of cancer cells without dramatically affecting normal cells. The synthesis of a useful and stable natriuretic peptide can enhance the effect of cancer treatments and significantly reduce drug resistance and toxicity."

Journal • Review • Breast Cancer • Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] EFFECTS OF NESIRITIDE, SERELAXIN, AND ULARITIDE IN ACUTE HEART FAILURE: META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (ACC 2021) - "Our meta-analysis showed that Nesiritide, Serelaxin, and Ularitide did not appear to confer clinical benefit in terms of mortality and heart failure admission in patients with acute heart failure. Our findings further revealed that hypotension was common in these agents’ effects when compared to placebo treatments."

Retrospective data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension

ULA04: Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide. (clinicaltrials.gov) - P2; N=38; Recruiting; Sponsor: University of Aarhus; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

Natriuretic peptides in diagnostics and therapy. (PubMed, Pol Merkur Lekarski) - "Eight natriuretic peptides have been described so far: ANP, BNP, CNP, DNP, urodilatin, uroguanylin, osteocrin, musculin and three receptors: NPR-A, NPR-B and NPR-C thanks to which these hormones accomplish their physiological functions...These drugs are mainly used among patients with heart failure. Research is currently underway on the efficacy and safety of other synthetic natriuretic peptides."

Journal • Review • Acute Coronary Syndrome • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Embolism

[VIRTUAL] Effects of different treatment regimens on high sensitive troponin T and NT-proBNP in patients with acute decompensated heart failure (HEART FAILURE-I 2020) - "The aim of this prospective study was to evaluate the effects of positive inotropic agents (dobutamine, levosimendan), vasodilators (ularitide) and loop diuretics (furosemide) on hs-TnT and NT-proBNP in patients with acute cardiac decompensation. Increased hs-TnT in patients treated with positive inotropic drugs was associated with increased mortality and re-hospitalization rate compared to the reference group with intravenous diuretic therapy and the group treated with vasodilator ularitide. NT-proBNP decreased in all groups, but without significant association with cardiac events."

Clinical • Cardiovascular • Dyslipidemia

ULA04: Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide. (clinicaltrials.gov) - P2; N=38; Not yet recruiting; Sponsor: University of Aarhus; Trial completion date: May 2023 ➔ Aug 2023; Trial primary completion date: May 2022 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis

Emerging Therapies for Acute and Chronic Heart Failure: Hope or Hype? (PubMed) - J Pharm Pract - "Consequently, phase 3 trials are ongoing to evaluate the effect of serelaxin and ularitide on clinical outcomes. Given the poor history of recent investigational acute HF drugs that have advanced to phase 3/4 studies, enthusiasm for both serelaxin and ularitide must be tempered until these trials are completed."

Journal • Biosimilar • Heart Failure

"Original Article: Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure https://t.co/Up3BLbkOby"

Biosimilar • Cardiovascular • Heart Failure

Refractory abdominal fluid (ascites) in patients with liver cirrhosis, and the potential treatment with 48 hours infusion of ularitide; a salt and water excreting peptide. (clinicaltrialsregister.eu) - P2; N=38; Ongoing; Sponsor: Department of Hepatology and Gastroenterology, Aarhus University Hospital

Clinical • New P2 trial

ULA04: Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide. (clinicaltrials.gov) - P2; N=38; Not yet recruiting; Sponsor: University of Aarhus

Clinical • New P2 trial

Update on the diagnosis and management of acute heart failure. (PubMed, Curr Opin Cardiol) - "Despite many advances in understanding the pathophysiology of AHF, there is currently insufficient evidence to suggest changes to standards of care."

Biomarker • Journal

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure-Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline? (PubMed, J Clin Med) - "Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents."

Clinical • Journal • Review

Newer hormonal pharmacotherapies for heart failure. (PubMed, Expert Rev Endocrinol Metab) - "However, drugs targeting these novel pathways (aliskiren, tolvaptan, ularitide, serelaxin, bosentan, macitentan) failed to show mortality benefit...If proven to be efficacious in larger outcome trials, finerenone can be a valuable addition baseline HF therapy. More basic, translational, and phenotype specific clinical research is warranted to improve HF pharmacotherapy."

Journal

"Interesante aunque no hay diferencia con el placebo el ularitide. Estadisticamente sin diferencia" (@davichiopb7)

Clinical