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Evaluating ziltivekimab for treating heart failure with inflammation

Effects of Ziltivekimab Versus Placebo on Morbidity and Mortality in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Systemic Inflammation

Phase 3 Interventional Novo Nordisk A/S · NCT05636176

This study is testing if a new medication called ziltivekimab can help people with heart failure and inflammation feel better over the course of four years.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment5600 (estimated)
Ages18 Years and up
SexAll
SponsorNovo Nordisk A/S Industry-sponsored
Drugs / interventionsziltivekimab
Locations1117 sites (Alexander City, Alabama and 1116 other locations)
Trial IDNCT05636176 on ClinicalTrials.gov

What this trial studies

This study aims to assess the efficacy of ziltivekimab in treating individuals with heart failure and inflammation. Participants will receive either ziltivekimab or a placebo through monthly injections, using either a pre-filled syringe or a pen-injector. The study will span up to four years and involve up to 20 clinic visits, during which participants will use a mobile app to track their injections and complete questionnaires about their health. The primary focus is on measuring the impact of ziltivekimab on heart failure symptoms and inflammation markers.

Who should consider this trial

Good fit: Ideal candidates include individuals with heart failure who have elevated levels of inflammation as indicated by high-sensitivity C-reactive protein.

Not a fit: Patients without heart failure or those who do not exhibit elevated inflammation markers may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients suffering from heart failure and inflammation.

How similar studies have performed: While this approach is being explored, similar studies targeting inflammation in heart failure have shown promise, suggesting potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Serum high-sensitivity C-reactive protein (hs-CRP) greater than equal to 2 milligrams per liter (mg/L) at screening (visit 1) Disease specific - cardiovascular
* At least one of the following:

  1. N-terminal-pro-brain natriuretic peptide (NT-proBNP) greater than equal to 300 picograms per milliliter (pg/mL) at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NTproBNP must be greater than equal to 600 pg/mL. Note that the screening electrocardiogram (ECG) must be obtained the same day as sampling for NT-proBNP.
  2. Hospitalisation or urgent/unplanned visit with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the last 9 months prior to screening (visit 1) in combination with NT-proBNP greater than equal to 200 pg/mL at screening (Visit 1) for patients without ongoing atrial fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NT-proBNP must be greater than equal to 600 pg/mL.
* Diagnosis of heart failure (New York Heart Association \[classification\] \[NYHA\] Class II-IV).
* Left ventricular ejection fraction (LVEF) greater than 40 percentage (%) documented by echocardiography within 12 months prior to or at screening (visit 1). The LVEF must be documented in medical records and the most recent measurement must be used to determine eligibility with no interim event signalling potential deterioration in ejection fraction (e.g., myocardial infarction \[MI\] or heart failure \[HF\] hospitalisation).
* Structural heart disease and/or functional heart disease documented by echocardiography within 12 months prior to or at screening (visit 1) showing at least one of the following:
* Left atrial (LA) volume index greater than 34 milliliter per meter square (mL/m\^2).
* LA diameter greater than equal to 3.8 centimeter (cm).
* LA length greater than equal to 5.0 cm.
* LA area greater than equal to 20 cm square.
* LA volume greater than equal to 55 milliters (mL).
* Intraventricular septal thickness greater than equal to 1.1 cm.
* Posterior wall thickness greater than equal to 1.1 cm.
* Left ventricular (LV) mass index greater than equal to 115 grams per meter square (g⁄m\^2 ) in men or greater than equal to 95 g⁄m\^2 in women.
* E/e' (mean septal and lateral) greater than equal to 10.
* e' (mean septal and lateral) less than 9 centimeter per second (cm/s).
* No heart failure hospitalisations or urgent heart failure visits between screening (visit 1) and randomisation (visit 2).

Exclusion Criteria:

Medical conditions - cardiovascular

* Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart failure hospitalisation, within 30 days prior to screening (visit 1).
* Systolic blood pressure greater than equal to 180 millimeters of mercury (mmHg) at screening (visit 1). If the systolic blood pressure is 160-179 mmHg, the patient should be receiving greater than equal to 3 antihypertensive drugs. (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
* Heart rate above 110 or below 40 beats per minute as evaluated on the electrocardiogram (ECG) performed at screening (visit 1) (Note: Potential participants may be retested for this criterion within the visit window and without rescreening, at the discretion of the investigator).
* Planned coronary, carotid or peripheral artery revascularisation known during the screening period (visit 1). (Note: Planned coronary angiogram is not exclusionary).
* Planned cardiac device or atrial flutter/atrial fibrillation ablation procedure known during the screening period (visit 1).
* Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2).
* Heart failure due to infiltrative cardiomyopathy (e.g., sarcoid, amyloid), arrhythmogenic right ventricular cardiomyopathy, Takutsubo cardiomyopathy, genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, uncorrected more than moderate primary valve disease.
* Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
* Any other condition judged by the investigator that could account for heart failure symptoms and signs (e.g., anaemia, hypothyroidism).

Medical conditions - infections/immunosuppression

\- Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.

Where this trial is running

Alexander City, Alabama and 1116 other locations

+1067 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Heart Failure
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.