Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

All Conditions

Cardiotoxicity

Personal history, physical examination including anthropometry with hip/waist-ratio, electrocardiogram, echocardiography, 1-minute-sit-to-stand test, questionnaires on health-related quality of life (SF-36), diet, physical activity, and fatigue

cardiac assessment

Claudia E Kuehni, MD

Christina Schindera, MD

Gabriela Kuster, MD

Stephan Dobner, MD

Thomas Suter, MD

Nana K Poku, MD

Reto Kurmann, MD

Eva Scheler, MD

This multicenter, prospective cohort study evaluates early cardiac dysfunction in adult survivors of childhood cancer. The hypothesis of this study is that cardiac dysfunction can be detected earlier when using speckle tracking echocardiography as novel echocardiographic technique compared to conventional echocardiography.

Cardiovascular disease including cardiac dysfunction is the leading non-malignant cause of death in childhood cancer survivors. Early detection of cardiac dysfunction is important to identify those in need for medical intervention to improve outcome. This study invites adult childhood cancer survivors to a clinical appointment to the University Hospital Bern, Switzerland. A detailed, standardized cardiac assessment including conventional and novel echocardiographic techniques (speckle tracking) as well as cardiopulmonary exercise testing is performed. Cardiac dysfunction is evaluated in survivors who have had cardiotoxic cancer therapy with anthracyclines and/or chest radiation (high risk) and in survivors who have had chemotherapy other than anthracyclines (standard risk).

Cardiac Dysfunction in Childhood Cancer Survivors

Prospective Single Center Cohort Study for Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors

Conventional echocardiography: left ventricular ejection fraction (%)

Speckle tracking echocardiography: longitudinal (LS), circumferential (CS), and radial strain (RS)

Cardiopulmonary exercise testing: peak oxygen consumption, percent-predicted carbon dioxide production

Cumulative doses of anthracyclines, steroids, and alkylating agents (mg/m2)

University Hospital, Basel, Switzerland

University Children's Hospital Basel

Insel Gruppe AG, University Hospital Bern

Cantonal Hospital of St. Gallen

Luzerner Kantonsspital

University Hospital, Geneva

University of Bern

Neoplasms

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Angiotensin Receptor Antagonists

Enzyme Inhibitors

Angiotensin-Converting Enzyme Inhibitors

Mineralocorticoid Receptor Antagonists

Mineralocorticoids

For patients randomized to vericiguat, a starting dose of 2.5mg will be initiated at the randomization visit. At pre-specified titration visits, subjects will be up-titrated to vericiguat 5mg and then to the target dose of vericiguat 10mg using titration criteria based on mean systolic blood pressure and evaluation for clinical symptoms. Vericiguat will be administered in the background of optimal medical therapy for cardiomyopathy/heart failure.

For patients randomized to the control group, optimal medical therapy for cardiomyopathy/heart failure will be instituted throughout the study period.

A starting dose of vericiguat 2.5 mg will be administered in-clinic at the Day 1 visit. Titration visits will occur on Days 14 and 28, with dose escalation to 5 mg and 10 mg.

Vericiguat

All subjects will be followed by a cardiologist throughout the study period and will receive optimal medical therapy for cardiomyopathy/heart failure following the ACCF/AHA and ESC Guidelines for the Management of Heart Failure recommendations, applied individually at the discretion of the treating investigator and in line with individual tolerability. This includes medications such as ßblockers, angiotensin converting enzyme inhibitors(ACEI), angiotensin receptor/neprilysin inhibitor (ARNI), angiotensin receptor blockers (ARB), and mineralocorticoid antagonists

Optimal medical therapy

Anthony Yu, MD

Jennifer Liu, MD

Anthony Yu, MD, MS

The purpose of this study is to find out if adding vericiguat to standard treatment for cancer therapy related cardiac dysfunction (CTRCD) is more effective than standard treatment alone. The addition of vericiguat to the usual treatment could help improve cardiac function, but it could also cause side effects. This study will help researchers find out whether this different treatment is better, the same as, or worse than the usual approach.

This is a single center, open-label, randomized controlled trial of vericiguat in adult patients with breast cancer and Cancer Therapy-Related Cardiac Dysfunction (CTRCD).

A Study of Vericiguat in People With Breast Cancer and Cancer Therapy-Related Cardiac Dysfunction

A Randomized Controlled Trial of the Soluble Guanylate Cyclase Stimulator Vericiguat in Patients With Breast Cancer and Cancer Therapy-Related Cardiac Dysfunction (ELEVATE)

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

For the primary analysis, intervention effect will be evaluated by comparing differences in mean VO2peak changes from baseline to month 6 between the investigational and control groups using the analysis of covariance approach (ANCOVA).

assessed by the number of participants with a change in VO2peak ≥ 1.32 ml O2 • kg-1 • min-1 (technical error of CRF measurement) from baseline to month 6. A change in VO2peak ≥ 1.32 ml O2 • kg-1 • min-1 will be considered a response, whereas a change in VO2peak \< 1.32 ml O2 • kg-1 • min-1 will be considered a non-response.

Merck Sharp & Dohme LLC

Memorial Sloan Kettering Cancer Center

Heart Failure

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Niacinamide

Niacin

Nicotinic Acids

Folic Acid

Vitamin B Complex

Trace Elements

Hypolipidemic Agents

Antimetabolites

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

The patients randomised into this arm of the trial will receive 500 mg Nicotinamide Riboside b.i.d. The duration of blinded therapy will depend on the duration of anthracycline therapy, and will for some patients last for 3 months, others for 6 months.

The patients randomised into this arm of the trial will receive a matching placebo b.i.d. The duration of treatment is equivalent to the description in the treatment arm.

Nicotinamide Riboside 500mg b.i.d as long as the patient is receiving anthracycline therapy

Nicotinamide Riboside

Matching placebo b.i.d as long as the patient is receiving anthracycline therapy

Placebo

Torbjørn Omland, MD, PhD

Victoria Vinje, MD

Jürgen Geisler, MD, PhD

Evandro F Fang, PhD

Breast cancer is the most common form of cancer in women. Modern breast cancer treatments have led to increased survival, but at the same time, increased risk for cardiotoxicity and development of heart failure. In this study, the investigators want to evaluate whether nicotinamide riboside can prevent cancer-related cardiac dysfunction in metastatic breast cancer patients scheduled for anthracycline therapy. Further, the investigators will evaluate change in signs of skeletal muscle injury and functional capacity.

The trial is prospective, randomised, double-blind and placebo-controlled. The primary objective is change in left ventricular ejection fraction (LVEF), determined by cardiac MRI (CMR). Secondary objectives are change in circulating high-sensitivity cardiac troponin I and T (hs-TnI and hs-TnT), Creatine Kinase (CK) and myoglobin, and various measurements of change in left ventricular systolic function determined by CMR and echocardiography. Additional assessments are evaluation of the patient's functional capacity and the patients will be asked to fill out questionnaires to assess quality of life.

60 patients will be randomised in a 1:1 ratio. The duration of blinded therapy will depend on the duration of anthracycline therapy. All patients will be examined at baseline and 3 months, and if the patient is scheduled for extended anthracycline therapy, an additional examination will be performed at 6 months.

Double-blind, randomised, placebo-controlled

The IMP and matching placebos will be provided by the manufacturers of ChromaDex. The Data Safety Committee will have the treatment allocation list.

Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients

Effect of Nicotinamide Riboside on Myocardial and Skeletal Muscle Injury and Function in Patients With Metastatic Breast Cancer Receiving Anthracyclines

Changes in the amount of circulating NAD+ will be measured using commercial kits and Liquid chromatography-mass spectrometry analyses (LC-MS analyses)

Change in transverse relaxation time (T2) measured by CMR

Change in longitudinal relaxation time (T1) measured by CMR

Change in left ventricular diastolic function as measured by echocardiography

Change in the aortic pulse wave velocity measured by CMR

Chance in circulating N-terminal pro b-type natriuretic peptide (NT-proBNP)

Chance in circulating cardiac myosin binding protein C (cMyC)

Change in circulating creatine kinase (CK)

Quality of life measured by Chalder Fatigue Scale. Items are rated on a 4-point Likert scale (0 = better than usual, 1 = no more than usual, 2 = worse than usual, 3 = much worse than usual), with higher scores indicating greater fatigue.

Quality of life measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Range in score from 0 to 100. A high scale score represents a higher response level.

Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / Quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Quality of life measured by European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L). Each dimension in the EQ-5D-5L has five response levels: no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5). There are 3,125 possible health states defined by combining one level from each dimension, ranging from 11111 (full health) to 55555 (worst health).

Change in left ventricular ejection fraction (LVEF), as determined by CMR from randomization to end of blinded therapy.

From randomization to the end of blinded therapy:

Change in LVEF, as determined by echocardiography

From randomization to the end of blinded therapy:

Change in left ventricular global longitudinal strain (GLS), as determined by echocardiography

From randomization to the end of blinded therapy:

Change in left ventricular global circumferential strain (GCS) and GLS, as determined by CMR

From randomization to the end of blinded therapy:

Change in left ventricular end-systolic volume measured by CMR

From randomization to the end of blinded therapy:

Change in circulating hs-cTnT

From randomization to the end of blinded therapy:

Change in circulating hs-cTnI

From randomization to the end of blinded therapy:

Change in distance in meters during 6-minute walk test

From randomization to the end of blinded therapy:

Change in force generated by handgrip strength test

ChromaDex, Inc.

Norwegian Cancer Society

Norwegian Breast Cancer Association

Helse Sor-Ost

University Hospital, Akershus

Professor

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Coronary Artery Disease

Peripheral Arterial Disease

Diabetes Mellitus

Hypertension

Cardiomyopathies

Ischemia

Coronary Disease

Myocardial Ischemia

Peripheral Vascular Diseases

Vascular Diseases

Arteriosclerosis

Arterial Occlusive Diseases

Atherosclerosis

In this group, physicians will use standard care plus the clinical decision aid.

In this group, physicians will use standard care only.

The clinical decision aid tool will be used at the subject's first visit (Week 0), Week 12 and Week 24.

Clinical Decision Aid

Cardiology clinic visits will take place at the subjects first visit (Week 0), Week 12 and Week 24.

Standard Care

Sherry-Ann Brown, MD, PhD

This is a single-center, double-arm, open-label, randomized feasibility study that will determine whether a novel clinical decision aid accessed via the electronic health record will be acceptable to both cancer survivors and their cardiologists, will favorably impact appropriate medication use and cardiac imaging surveillance, and will improve clinician and patient decision-making, perception, and behavior towards cardioprotective medication usage and cardiovascular disease imaging utilization.

For this feasibility study, the researchers will create the clinical decision aid and test the central hypothesis that this novel clinical decision aid accessed via the electronic health record will be acceptable to both cancer survivors and their cardiologists and will favorably impact appropriate medication use and cardiac imaging surveillance. The hypothesis is supported by preliminary data suggesting that an initial and rudimentary version of the clinical aid increases appropriate medication use and imaging follow-up in cardio-oncology patients. Success will be determined by ≥85% of clinic visits using the clinical decision aid resulting in pursuit of medication use and cardiac imaging surveillance patterns commensurate with recommendations specific to cancer survivors, with overall rates the same or higher than the group without the clinical decision aid, as well as overall favorable patient and physician focus group comments and survey responses.

PAtient Similarity for Decision-Making in Prevention of Cardiovascular Toxicity (PACT): A Feasibility Study

The number of subjects in which medication use pursued is consistent with current medical society recommendations appropriate for the subject.

The number of subjects in which imaging surveillance pursued is consistent with current medical society recommendations appropriate for the subject.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cardiac Dysfunction in Childhood Cancer Survivors	NCT03790943	Cardiac Dysfunc... Cardiovascular ... Childhood Cance...	cardiac assessm...	18 Years -	University of Bern
A Study of Vericiguat in People With Breast Cancer and Cancer Therapy-Related Cardiac Dysfunction	NCT05806138	Breast Cancer Cardiac Dysfunc...	Vericiguat Optimal medical...	18 Years -	Memorial Sloan Kettering Cancer Center
A Study of Vericiguat in People With Breast Cancer and Cancer Therapy-Related Cardiac Dysfunction	NCT05806138	Breast Cancer Cardiac Dysfunc...	Vericiguat Optimal medical...	18 Years -	Memorial Sloan Kettering Cancer Center
Nicotinamide Riboside and Prevention of Cancer Therapy Related Cardiac Dysfunction in Breast Cancer Patients	NCT05732051	Breast Cancer Metastatic Brea... Cancer Therapy-... Cardiotoxicity Heart Failure	Nicotinamide Ri... Placebo	18 Years -	University Hospital, Akershus
Cardiac Dysfunction in Childhood Cancer Survivors	NCT03790943	Cardiac Dysfunc... Cardiovascular ... Childhood Cance...	cardiac assessm...	18 Years -	University of Bern
PAtient Similarity for Decision-Making in Prevention of Cardiovascular Toxicity (PACT): A Feasibility Study	NCT05377320	Heart Failure Coronary Artery... Peripheral Arte... Ischemia Hypertension Diabetes Mellit... Cardiomyopathie... Cardiotoxicity	Clinical Decisi... Standard Care	18 Years -	Medical College of Wisconsin

Spots Global Cancer Trial Database for cardiac dysfunction