CK-4021586 for Heart Failure
(AMBER-HFpEF Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Cytokinetics
Must be taking: Beta-blockers, ACE/ARB, SGLT2-inhibitors, GLP-1 agonist
Disqualifiers: Malignancy, Active infection, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is a Phase 2 dose-finding study in adult participants with symptomatic HFpEF.
Will I have to stop taking my current medications?
The trial requires that if you are taking beta-blockers, ACE/ARB, ARNI, or SGLT2-inhibitors, you must be on a stable dose for more than 4 weeks before joining. If you're on a GLP-1 agonist, you need to be on a stable dose for more than 24 weeks with no plans to change it during the study.
What data supports the effectiveness of the drug CK-4021586 for heart failure?
The research highlights that new pharmacological agents, like those in the same class as CK-4021586, have shown effectiveness in reducing mortality and improving outcomes in heart failure patients. These agents, including SGLT2 inhibitors and ARNI, have demonstrated benefits in various types of heart failure, suggesting potential effectiveness for CK-4021586.
12345Eligibility Criteria
Adults aged 40-85 with symptomatic heart failure (HFpEF), having a left ventricular ejection fraction (LVEF) ≥60% and classified as NYHA functional class II or III. Participants must have stable doses of certain heart medications for at least 4 weeks, a BMI under 40 kg/m2, and specific levels of NT-proBNP depending on their rhythm status.Inclusion Criteria
Screening echocardiography with LVEF ≥ 60%
I have heart failure and my symptoms are mild to moderate.
Body mass index < 40 kg/m2
+4 more
Exclusion Criteria
History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion
Other protocol-defined Inclusion/Exclusion criteria apply.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive CK-4021586 or placebo daily, guided by echocardiography assessments, for 12 weeks
12 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The AMBER-HFpEF trial is testing the safety and tolerability of different doses of CK-4021586 compared to a placebo in patients with HFpEF. This Phase 2 study aims to find the right dose by randomly assigning participants to receive either the drug or placebo.
6Treatment groups
Experimental Treatment
Placebo Group
Group I: CK-4021586 - Cohort 3Experimental Treatment1 Intervention
Participants may receive 450 mg or 600 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
Group II: CK-4021586 - Cohort 2Experimental Treatment1 Intervention
Participants may receive 300 mg or 450 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
Group III: CK-4021586 - Cohort 1Experimental Treatment1 Intervention
Participants may receive 150 mg or 300 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
Group IV: Placebo - Cohort 3Placebo Group1 Intervention
Participants will receive placebo daily for up to 12 weeks.
Group V: Placebo - Cohort 2Placebo Group1 Intervention
Participants will receive placebo daily for up to 12 weeks.
Group VI: Placebo - Cohort 1Placebo Group1 Intervention
Participants will receive placebo daily for up to 12 weeks.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Linder Center for Research & Education at the Christ HospitalCincinnati, OH
Loading ...
Who Is Running the Clinical Trial?
CytokineticsLead Sponsor
References
Renal effects of guideline-directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology. [2022]Novel pharmacologic treatment options reduce mortality and morbidity in a cost-effective manner in patients with heart failure (HF). Undisputedly, the effective implementation of these agents is an essential element of good clinical practice, which is endorsed by the European Society of Cardiology (ESC) guidelines on acute and chronic HF. Yet, physicians struggle to implement these therapies as they have to balance the true and/or perceived risks versus their substantial benefits in clinical practice. Any worsening of biomarkers of renal function is often perceived as being disadvantageous and is in clinical practice one of the most common reasons for ineffective drug implementation. However, even in this context, they clearly reduce mortality and morbidity in HF with reduced ejection fraction (HFrEF) patients, even in patients with poor renal function. Furthermore these agents are also beneficial in HF with mildly reduced ejection fraction (HFmrEF) and sodium-glucose cotransporter 2 (SGLT2) inhibitors more recently demonstrated a beneficial effect in HF with preserved ejection fraction (HFpEF). The emerge of several new classes (angiotensin receptor-neprilysin inhibitor [ARNI], SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) and the recommendation by the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic HF of early initiation and titration of quadruple disease-modifying therapies (ARNI/angiotensin-converting enzyme inhibitor + beta-blocker + mineralocorticoid receptor antagonist and SGLT2 inhibitor) in HFrEF increases the likelihood of treatment-induced changes in renal function. This may be (incorrectly) perceived as deleterious, resulting in inertia of starting and uptitrating these lifesaving therapies. Therefore, the objective of this consensus document is to provide advice of the effect HF drugs on renal function.
Recent advances in the pharmacological therapy of chronic heart failure: Evidence and guidelines. [2022]Heart failure (HF) is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and associated with elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. It is classified according to left ventricular ejection fraction (LVEF): HF with reduced EF (HFrEF) with an LVEF of ≤40%, HF with mildly reduced EF (HFmrEF) with an LVEF of 41 to 49%, HF with preserved EF (HFpEF) with an LVEF of ≥50%, and HF with improved EF (HFimpEF) with a baseline LVEF of ≤40%, a ≥ 10% increase from baseline LVEF, and a second measurement of LVEF of >40%. Despite the remarkable progress in the management of HF over the past decades, its prognosis is still poor with higher rates of mortality and hospitalization due to worsening HF. Therefore, the development of novel strategies including pharmacologic therapy is needed to further improve its prognosis. Recent large-scale clinical trials have demonstrated the efficacy of newer pharmacological agents including angiotensin II receptor/neprilysin inhibitor (ARNI), sacubitril/valsartan, type 2 sodium-glucose cotransporter (SGLT2) inhibitors, dapagliflozin, empagliflozin and sotagliflozin, and soluble guanylyl cyclase (sGC) stimulator, vericiguat, and cardiac myosin activator, omecamtiv mecarbil. This review focuses the recent advances in the pharmacological agents for treatment of chronic heart failure, including their mechanisms of action, the evidence based on the clinical trials, and the guideline recommendations for their use.
[Chronic heart failure : current guideline recommendations and innovations]. [2018]Chronic heart failure is one of the most common chronic diseases worldwide with increasing prevalence and incidence. Due to the high morbidity and mortality a standardized and evidence-based therapy is essential. The present article gives an overview of the innovations from 2014 based on the current guidelines of the European Society of Cardiology. First, improvements of established medication regimens regarding beta blockers, mineralocorticoid receptor antagonists and treatment options for heart rate reduction and disease management programs will be explained. Second, new pharmacological developments, such as the new substance class of angiotensin receptor blockers and neprilysin inhibitors (ARNI), will be presented. Finally, new insights into common comorbidities of chronic heart failure patients, such as atrial fibrillation and hyperkalemia will be discussed.
Pharmacology of heart failure: From basic science to novel therapies. [2021]Chronic heart failure is one of the leading causes for hospitalization in the United States and Europe, and is accompanied by high mortality. Current pharmacological therapy of chronic heart failure with reduced ejection fraction is largely based on compounds that inhibit the detrimental action of the adrenergic and the renin-angiotensin-aldosterone systems on the heart. More than one decade after spironolactone, two novel therapeutic principles have been added to the very recently released guidelines on heart failure therapy: the HCN-channel inhibitor ivabradine and the combined angiotensin and neprilysin inhibitor valsartan/sacubitril. New compounds that are in phase II or III clinical evaluation include novel non-steroidal mineralocorticoid receptor antagonists, guanylate cyclase activators or myosine activators. A variety of novel candidate targets have been identified and the availability of gene transfer has just begun to accelerate translation from basic science to clinical application. This review provides an overview of current pharmacology and pharmacotherapy in chronic heart failure at three stages: the updated clinical guidelines of the American Heart Association and the European Society of Cardiology, new drugs which are in clinical development, and finally innovative drug targets and their mechanisms in heart failure which are emerging from preclinical studies will be discussed.
Improving quality of care and outcomes for heart failure. -Role of registries-. [2022]Heart failure (HF) results in substantial morbidity, mortality, and costs, yet quality of care varies widely and is frequently inadequate. Performance improvement registries have been developed to improve the quality of care and outcomes for patients with HF in both the inpatient and outpatient settings. HF registries in the United States include ADHERE, OPTIMIZE-HF, GWTG-HF, and IMPROVE HF. These registries collect data on clinical characteristics, admission, hospital, discharge, and/or outpatient care, as well as outcomes. Web-based tools that provide real-time feedback of performance and other quality measures benchmarked to other sites and national data are frequently utilized. Process-of-care improvement tools, including evidence-based clinical decision support, customizable order sets, and patient education are also used. Participation in performance improvement registries has been associated with substantial improvements in the use of guideline-recommended therapies for HF in both the inpatient and outpatient settings. Conformity with HF quality measures has also been shown to improve and disparities in care have also been reduced or eliminated. There have also been improvements in clinical outcomes. This paper reviews the evidence that participation in HF performance improvement registries is associated with improved use of guideline-recommended HF therapies, better conformity with quality measures, and improved outcomes in patients with HF.