cimlanod (BMS986231) / BMS - LARVOL DELTA

Exploring the clinical and mechanistic impacts of the nitroxyl donors on heart failure management: a meta-analysis of hemodynamics effects and safety (ESC-WCC 2025) - "This meta-analysis synthesizes evidence from 4 pivotal studies investigating the safety and hemodynamic effects of Cimlanod in this population...While no significant effects on mortality or major adverse events have been found, careful individual use with appropriate monitoring is advised. Although the treatment appears safe, additional studies with larger sample sizes must validate these findings."

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

An unexpected degradation pathway of N-hydroxy-5-methylfuran-2-sulfonamide (BMS-986231), a pH sensitive prodrug of HNO, in a prototype formulation solution. (PubMed, J Pharm Sci) - "A plausible mechanism was postulated for the unexpected degradation pathway of Cimlanod. This study provided in-depth stability knowledge of Cimlanod, which will be beneficial to the subsequent stability indicating method development and validation as well as the registrational applications on the content and qualification of impurities in new drug products."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

New cimlanod trial provides insights into mechanistic effects of vasodilators in heart failure. (PubMed, Eur J Heart Fail) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Impact of vasodilators on diuretic response in patients with congestive heart failure: a mechanistic trial of cimlanod (BMS-986231). (PubMed, Eur J Heart Fail) - "For patients with heart failure and congestion, vasodilation with agents such as cimlanod reduces the response to diuretic agents, which may offset any benefit from acute reductions in cardiac preload and afterload."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

An Investigational Study of Experimental Medication BMS-986231 Given in Participants With Different Levels of Liver Function (clinicaltrials.gov) - P1; N=74; Completed; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Completed; N=32 ➔ 74; Trial completion date: Mar 2019 ➔ Aug 2019; Trial primary completion date: Feb 2019 ➔ Aug 2019

Clinical • Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Gene Therapies • Heart Failure • CGB

Hemodynamic Effects of the Nitroxyl Donor Cimlanod (BMS-986231) in Chronic Heart Failure: A Randomized Trial. (PubMed, Eur J Heart Fail) - "In patients with chronic HFrEF, the hemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Stand [Up] and Stand by for New Strategies for Treating Acute Heart Failure. (PubMed, JACC Heart Fail) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study. (PubMed, JACC Heart Fail) - P2b | "Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325)."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension

[VIRTUAL] A Randomized, Double-blind, Placebo-controlled, Cross-over Phase 2 Study Of Intravenous Infusions Of BMS-986231 In Patients With Heart Failure And Impaired Systolic Function (StandUP-Kidney) (HFSA 2020) - "Conclusions : Compared to placebo, short-term infusion of cimlanod reduces the diuretic effect of furosemide and causes plasma volume expansion. These effects may be mediated by vasodilatation and a fall in renal perfusion pressure."

Clinical • Late-breaking abstract • P2 data • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension • Renal Disease

Rationale and design for the development of a novel nitroxyl donor in patients with acute heart failure. (PubMed, Eur J Heart Fail) - "In this manuscript, we describe the ongoing phase II development programme for BMS-986231, which consists of three related randomised placebo-controlled clinical trials, StandUP-AHF, StandUP-Imaging and StandUP-Kidney, which are designed to provide evidence of tolerability and efficacy as well as confirm the anticipated physiological effects in patients with heart failure with reduced ejection fraction. These studies will set the stage for the further study of BMS-986231 in future phase III clinical trials."

Clinical • Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure

A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS-986231 in Healthy Volunteers. (PubMed, J Clin Pharmacol) - "BMS-986231 was safe and well-tolerated for up to 24 hours (15 μg/kg/min) or 48 hours (10 μg/kg/min), with a favorable hemodynamic profile observed. Ongoing studies continue to evaluate the potential benefit of BMS-986231 in patients with acute heart failure."

Clinical • Journal • P1 data • Cardiovascular • Congestive Heart Failure • Heart Failure

A Study of Continuous Infusions of HNO (Nitroxyl) Donor in Patients With Heart Failure and Impaired Systolic Function (clinicaltrials.gov) - P2; N=49; Completed; Sponsor: Bristol-Myers Squibb; N=185 ➔ 49

Clinical • Enrollment change • Cardiovascular • Congestive Heart Failure • Heart Failure

STANDUP AHF: Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure (clinicaltrials.gov) - P2b; N=310; Recruiting; Sponsor: Bristol-Myers Squibb; Trial primary completion date: Nov 2018 ➔ May 2019

Trial primary completion date • Biosimilar • Cardiovascular • Heart Failure

A Study of Continuous Infusions of HNO (Nitroxyl) Donor in Patients With Heart Failure and Impaired Systolic Function (clinicaltrials.gov) - P2; N=42; Not yet recruiting; Sponsor: Bristol-Myers Squibb

New P2 trial • Biosimilar • Cardiovascular • Heart Failure

[VIRTUAL] HEMODYNAMIC EFFECTS OF NITROXYL DONOR BMS-986231 COMPARED TO NITROGLYCERIN OR PLACEBO IN PATIENTS WITH CHRONIC HEART FAILURE-A RANDOMIZED DOUBLE-BLIND CROSSOVER TRIAL (ACC 2020) - "In stable HFrEF, BMS-986231 does not appear to have an inotropic effect. Both BMS-986231 and NTG improve diastolic function compared to placebo. Ongoing trials of BMS-986231 will further define its potential role in the treatment of heart failure."

Clinical

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

STANDUP AHF: Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure (clinicaltrials.gov) - P2b; N=331; Completed; Sponsor: Bristol-Myers Squibb; Trial completion date: Jun 2019 ➔ Nov 2019

Clinical • Trial completion date

An Investigational Study of Continuous 8-Hour Intravenous Administrations of BMS-986231 in Participants With Heart Failure and Reduced Heart Function Given a Standard Dose of Loop Diuretic (clinicaltrials.gov) - P2; N=23; Completed; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Completed

Clinical • Trial completion

STANDUP AHF: Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure (clinicaltrials.gov) - P2b; N=331; Completed; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Completed; Trial completion date: Nov 2019 ➔ Jun 2019

Clinical • Trial completion • Trial completion date

An Investigational Study of Continuous 8-Hour Intravenous Administrations of BMS-986231 in Participants With Heart Failure and Reduced Heart Function Given a Standard Dose of Loop Diuretic (clinicaltrials.gov) - P2; N=20; Active, not recruiting; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Active, not recruiting

Enrollment closed

A Pharmacokinetics, Safety and Tolerability Study of Multiple Formulations of BMS-986231 in Healthy Participants (clinicaltrials.gov) - P1; N=60; Completed; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Pharmacokinetics, Safety and Tolerability Study of Multiple Formulations of BMS-986231 in Healthy Participants (clinicaltrials.gov) - P1; N=49; Active, not recruiting; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study of Continuous Infusions of HNO (Nitroxyl) Donor in Patients With Heart Failure and Impaired Systolic Function (clinicaltrials.gov) - P2; N=185; Completed; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Completed; N=42 ➔ 185

Clinical • Enrollment change • Trial completion

A Dose Ranging Phase IIa Study of 6 Hour Intravenous Dosages of CXL-1427 in Patients Hospitalized With Heart Failure (clinicaltrials.gov) - P2a; N=70; Completed; Sponsor: Bristol-Myers Squibb; N=46 ➔ 70

Clinical • Enrollment change

STANDUP AHF: Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure (clinicaltrials.gov) - P2b; N=310; Recruiting; Sponsor: Bristol-Myers Squibb; Trial completion date: Aug 2019 ➔ Nov 2019

Trial completion date