Symptoms and General Pathology

All Conditions

Heart and Blood Diseases

Substance Related Disorders

Wounds and Injuries

Ischemia

Cardiotoxicity

Reperfusion Injury

Myocardial Reperfusion Injury

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Remote ischaemic conditioning in the form of a blood pressure cuff on upper arm inflated upto 200 mm Hg (or systolic BP + 20 mm Hg if low platelets e.g. 50-150 x10\^9/L, skip remote ischaemic conditioning (RIC) if platelets \< 50 x 10\^9/L) for 5 minutes, then deflated to 0 mm Hg for 5 minutes, for 4 cycles before beginning of chemotherapy infusion. The entire pre-conditioning phase will last 40 minutes.

Blood pressure cuff on upper arm inflated to 10 mm Hg for 5 minutes, then deflated to 0 mm Hg for 5 minutes, for 4 cycles before beginning of chemotherapy infusion. The entire control comparator will last 40 minutes

each cycle of Remote Ischaemic Conditioning (RIC) consists of inflating a blood pressure cuff on the upper limb (arm) upto 200mm Hg (systolic BP + 20 mm Hg for low platelets, e.g. 50-150 x 10\^9/L; skip RIC if platelets \< 50 x 10\^9/L) for 5 minutes, then deflated to 0 mm Hg for 5 minutes.

Remote Ischaemic Conditioning

Sham control blood pressure cuff placement at 10 mm Hg for 5 minutes, then deflated to 0 mm Hg for 5 minutes.

Placebo

Robin Chung, MBBS MRCP

Michael Mallouppas, MBBS MRCP

Michael Mallouppas, MRCP

Derek M Yellon, DSc FACC FAHA

Malcolm Walker, MD FRCP

Alison Macklin, BSc

Derek M Yellon, PhD FACC FAHA

Alison Macklin

Cancer survival has improved steadily due to earlier detection and treatment. Despite the established efficacy of anthracycline chemotherapy, its damaging effects on the heart (cardiotoxicity) limits treatment and confers acute and long term adverse cardiovascular consequences. Protective strategies for the heart (cardioprotection) with iron binders (chelation), heart rate (beta blockade) and blood pressure (renin angiotensin inhibition) medications have demonstrated promise in adult cancer patients, but these treatments are typically prescribed only after significant changes in heart chamber size and pumping ability are detected by imaging investigations (myocardial dysfunction).

Furthermore, these conventional therapies are constrained by important side effects that affect bone marrow, blood pressure, and the kidneys.

Remote ischaemic conditioning (RIC) protects the heart by activating cell survival pathways through brief repeated inflations and deflations of a blood pressure cuff to limit blood flow temporarily (noninjurious ischaemia). These innate survival mechanisms prevent part of the cellular injury that occurs during the ischaemia reperfusion cascade during a heart attack (myocardial infarction). Ischaemia reperfusion injury also shares common biochemical pathways with anthracycline cardiotoxicity, and thus RIC may be a novel form of nonpharmacological cardioprotection that can be applied when undergoing anthracycline chemotherapy.

The investigators propose a pilot single centre randomised controlled trial to investigate the effect of RIC on reducing heart muscle damage (myocardial injury) in anthracycline-treated cancer patients. The investigators will assess subclinical myocardial injury using high-sensitivity blood tests (troponin T levels) and advanced imaging techniques, monitor heart rhythm disturbances (cardiac arrhythmia) and analyse metabolic changes in urine and blood during chemotherapy, at specified time points, and follow up to 5 years after completing chemotherapy treatment).

This pilot study aims to demonstrate whether remote ischaemic preconditioning (RIC), delivered as a nonpharmacological treatment via repeated inflations and deflations of a limb blood pressure cuff, can reduce subclinical myocardial injury from anthracycline chemotherapy. Chemotherapy cardiotoxicity is the dose limiting constraint in anthracycline chemotherapy regimens, and conventional drug treatments to prevent and treat it are limited by important interactions with blood pressure, kidney function or bone marrow function. The lifetime cancer risk is between 1 in 2 and 1 in 3 in the general population. Cancer treatment and survival has improved steadily 50% of patients now survive their initial cancer diagnosis, but approximately 25 to 50% of survivors will have abnormal cardiac function over the next twenty years. Historically, anthracycline chemotherapy dosing has been stratified to limit the incidence of clinical heart failure to around 5%. More recent studies have reported at least one third of anthracycline chemotherapy patients demonstrate a significant rise in Troponin levels as a blood biomarker of subclinical myocardial injury as well as documented evidence of biomarker rise even after a single cycle of chemotherapy, and thus the absolute threshold for myocardial injury may be lower and thus more prevalent than these conservative figures.

In standard dosing regimens, chemotherapy may be delayed or suspended in cancer patients based on the simplified measure of ejection fraction (EF) as a measure of cardiac systolic function. Conventional heart failure treatments such as betablockers or ACE inhibitors are usually prescribed only after a significant fall in EF, even though myocardial injury occurs long before this imprecise measurement changes. RIC has been shown to reduce myocardial injury and improve outcomes in elective and emergency percutaneous coronary intervention (PCI) and elective coronary artery bypass graft surgery (CABG). The common biochemical pathways in ischaemia reperfusion and anthracycline-induced cardiac myocyte injury suggest that RIC may be an unexplored nonpharmacological treatment to reduce myocardial injury for cancer patients.

This pilot study aims to demonstrate the effectiveness of RIC as an elegant noninvasive, nonmedicinal treatment to reduce myocardial injury in cancer patients, and therefore poses no significant ethical issues. RIC is known to be a safe intervention with no known significant adverse effects. Some patients have reported mild discomfort during cuff inflation. A small number have experienced minor skin bruising at the cuff site which is transient. There are no known long term adverse effects of RIC,

Recruitment Patients will be identified by their usual oncology team, and referred to the cardiology team based solely on known inclusion and exclusion criteria, which will ensure this process is free from undue influence.

The benefits of the study include an increase in the scientific understanding of how RIC may lead to a reduction in myocardial injury, as well as longitudinal documentation of myocardial injury in the form of blood biomarkers, ECG changes, metabolic changes, and novel imaging markers in cancer patients undergoing a common form of chemotherapy.

Effect of Remote Ischaemic Conditioning in Oncology Patients

A Single Centre Double-blinded Randomized Placebo Controlled Pilot Study Investigating the Effect of Remote Ischaemic preConditioning in ONCology Patients Undergoing Chemotherapy (ERIC-ONC)

Biomarker of myocardial injury using high-sensitivity Troponin-T for above time points as serial measurements.

Major Adverse Cardiovascular Event (myocardial infarction, clinical heart failure requiring admission, life-threatening arrhythmia atrioventricular (AV) block requiring pacemaker, cardiac or cancer death)

Echocardiographic longitudinal function (GLS %)

two weeks ambulatory electrocardiographic (ECG) monitoring for atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, atrioventricular block

for heart failure / raised left atrial pressure

Comparison of changes in micro ribonucleic acid (miRNA) and mitochondrial deoxyribonucleic acid (mtDNA), markers of protein expression at baseline (before) and at 3-months' follow up after completing chemotherapy regimen

University College London Hospitals

University College, London

Neoplasms

Skin and Connective Tissue Diseases

Immune System Diseases

Breast Neoplasms

Hypersensitivity

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Natriuretic Agents

Trastuzumab

Natriuretic Peptide, Brain

Patients with breast cancer beginning chemotherapy with a dose-dense regimen including adriamycin without concurrent trastuzumab.

Patients receiving trastuzumab in the adjuvant, neo-adjuvant, or metastatic setting in a regimen not containing simultaneous adriamycin therapy.

Joseph L Blackshear, M.D.

This pilot study involves very frequent monitoring of breast cancer patient blood levels of hs-cTnT Troponin and n-t-BNP (Brain Natriuretic Peptide) before and after initiation of chemotherapy with either adriamycin or trastuzumab in order to define the kinetics of both biomarkers during the first two cycles of chemotherapy. Cardiac troponins and BNP are frequently elevated after experimental chemotherapy in animal models. Their behavior in humans has been inconsistent, with occasional elevations seen, usually within 30 days of therapy. Assays for troponin with sensitivity into the pg/ml range have now been introduced. A majority of patients greater than age 50 have elevations above the detection limit, compared to only 1-3% with conventional troponin assays, and over 90% of diabetics have elevations above the detection limit. Moreover, augmented release of high sensitivity troponin is detected after exercise or rapid atrial pacing of durations of 10-15 minutes in patients with and without coronary artery disease. This improved sensitivity suggests the potential for detection and monitoring of cardiac damage after cancer chemotherapy. We hypothesized that this new generation of troponin assay would be associated with kinetic behavior suggesting ongoing cardiac damage with anthracycline therapy, and possibly also with trastuzumab.

Collect blood samples in two groups of patients (n=10 per group) for amino-terminal brain natriuretic peptide (n-t-BNP) and high sensitivity cardiac troponin T (hs-cTnT):

* Group 1 (adriamycin) will consist of patients beginning clinically indicated chemotherapy for breast cancer with a dose-dense (every 2 week) regimen. including adriamycin (n=10).
* Group 2 will include patients who receive trastuzumab in the adjuvant or (neo) adjuvant setting, or in a metastatic setting in a regimen that does not include simultaneous adriamycin.

Blood samples for hs-cTNT and n-t-BNP will be obtained on days pre-treatment, and post-treatment days 1, 2, 3, 7, pre-cycle 2, and post-cycle 2 days 1,2,3 and 7. The interval for treatment is usually two weeks for adriamycin and three weeks for trastuzumab. We will identify frequency of detectible levels above the detection limit and above the baseline, peak values and area under the curve. Enrollment of up to 15 per group will be allowed to guarantee acquisition of 10 full sets of samples. Lab draw from chemotherapy ports will be allowed. We plan to store specimens for future analyses with more sensitive assays in development.

Whole blood 10 ml per draw, yielding 5 ml of serum. After testing, the remaining serum will be stored.

Kinetics of Troponin and BNP in Breast Cancer Chemotherapy With Adriamycin and Trastuzumab

Pilot Study of the Kinetics of High Sensitivity Troponin and Brain Natriuretic Peptide in Breast Cancer Chemotherapy With Adriamycin and Trastuzumab

Descriptive statistics will be used to describe the quantitative values, and frequencies above and below the detection limit, time to peak, and amplitude of peak versus baseline values for both n-t-BNP and hs-cTnT.

Concentration-time plots from pre-treatment through days 1,2,3,7,and pre-cycle two

The difference between the pretreatment value and the highest level on days 1,2,3 or 7

Mayo Clinic

Principal Investigator

Diseases and Abnormalities at or Before Birth

Rare Diseases

Atherosclerosis

Congenital Abnormalities

Myocarditis

Arteriosclerosis

Arterial Occlusive Diseases

Vascular Diseases

Cardiomyopathies

Bone Density Conservation Agents

Immune Checkpoint Inhibitors

Calcium

Calcium, Dietary

* Electrocardiogram (ECG).
* Echocardiogram: A comprehensive evaluation of systolic and diastolic function, ventricular and atrial geometry will be performed. Special attention will be given to acquire a 3D measurement of left ventricular ejection fraction (LVEF) and to perform deformation imaging of left ventricle (global longitudinal strain (GLS)). The right ventricular function will be evaluated by tricuspid annular plane systolic excursion (TAPSE) and peak systolic velocity S' derived from color coded tissue Doppler imaging (TDI). Diastolic dysfunction will be based on average E/e' ratio \> 15 and left atrial (LA) area \> 30 cm2.

Cardiology consultation

Calcium score. This will be performed at baseline, 12 and 24 months. The scans at 12 and 24 months will be combined, if possible, with standard of care scans for cancer treatment.

Chest Computed Tomography (CT) without contrast

* FMD
* PAT

This aspect of the study will only be performed in the patients included by the Antwerp University Hospital due to organizational/practical issues.

Non-invasive endothelial function tests

An ECG will be taken prior to each ICI cycle during the first three months of treatment.

Electrocardiogram

An extra serum sample will be taken at baseline, 3, 6, 12, 24 months and in case of sudden cardiac problems. This will subsequently be analysed to determine high-sensitivity troponin I, high-sensitivity troponin T and NT-proBNP.

Extra serum sample (7.5 mL)

Christof Vulsteke, Prof

Danielle Delombaerde, PharmD

Hans Prenen, Prof

Sanne Wouters

Constantijn Franssen, Dr

The goal of this prospective, multicentre study is to investigate short- and long-term cardiovascular effects in cancer patients treated with immune checkpoint inhibitors (ICIs).

The main question\[s\] it aims to answer are:

* To investigate troponin and NT-proBNP values in patients receiving ICIs and their association with ICI-induced CV abnormalities and MACEs.
* Study the calcium score, systolic, and diastolic (dys)function.
* Evaluate associations between patient/disease characteristics / transthoracic echocardiography parameters / electrocardiography parameters and troponin / NT-proBNP levels.

Participants will be closely monitored by performing the following additional visits and testing:

* Chest CT scan prior to treatment start, after 12 and 24 months.
* Consultation with a cardiologist at baseline, 3, 6, 12 and 24 months, who will perform an electrocardiogram and echocardiogram.
* One additional blood sample prior to treatment start, after 3, 6, 12 and 24 months. An extra blood sample could be taken in case of sudden heart problems.
* Non-invasive endothelial function tests prior to treatment start, after 12 and 24 months.

The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular immune related adverse events (irAEs). The current guidelines are based on anecdotal evidence and expert opinions due to the lack of solid data and prospective studies. Therefore, cardiac monitoring, in patients receiving ICIs, is often not implemented by oncologists as many questions remain unanswered. Hence, the urgent need to investigate the possible short and long term cardiovascular effects of ICIs.

The investigators developed a multicentre, prospective study in which patients with a solid tumour eligible for ICI treatment will be enrolled. The study exists of routine investigations of blood parameters (troponin and (N-terminal) brain-type natriuretic peptide levels in particular) and a thorough cardiovascular follow-up on fixed time points during a period of two years. The cardiovascular follow-up consists of continuous remote patient monitoring, routine cardiology consultations including electrocardiograms, transthoracic echocardiograms, CT-scans for calcium scoring and non-invasive endothelial function tests. Associations between these blood parameters and short and long term cardiovascular irAEs will be statistically analysed.

This project will allow for a better estimate of the incidence of both short and long-term cardiovascular irAEs in a 'real world' patient population receiving ICIs. If the investigators are able to accurately predict and detect short- and long-term cardiovascular irAEs in an early (and subclinical) stage by correct implementation and interpretation of existing cardiac markers, they could be managed early on in a more effective manner.

Extensive CArdioVAscular Characterization and Follow-up of Patients Receiving Immune Checkpoint Inhibitors

Extensive CArdioVAscular Characterization and Follow-up of Patients Receiving Immune Checkpoint Inhibitors: a Prospective Multicentre Study

For the primary endpoint, the cumulative incidence of troponin elevation will be calculated with death as a competing risk. Cumulative incidences and corresponding 95% confidence intervals will be reported and a cumulative incidence plot will be used to visualize the results.

Cumulative incidences and 95% confidence intervals, considering death as a competing event.

Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual.

Joint model combining a linear mixed model for troponin and a sub-distributional proportional hazards model for the time-to-event taking into account death as a competing event for CV abnormality and MACE.

Cumulative incidences and 95% confidence intervals

Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual. This model will be extended with patient and treatment characteristics and their interaction with time, to evaluate their impact on the evolution of these parameters.

Bland-Altman curves and intraclass correlation coefficient (ICC) based on a two-way mixed effects model. The ICC and 95% confidence interval will be reported.

Flow mediated dilatation: dilatation % from baseline to maximal post-occlusion diameter.

Peripheral arterial tonometry ratio: based on the response to reactive hyperemia using post and pre-occlusion values

Algemeen Ziekenhuis Maria Middelares

Head of Integrated Cancer Center Ghent

Blood and Lymph Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Sarcoma

Wilms Tumor

Neuroblastoma

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Neoplasms, Connective and Soft Tissue

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Soft Tissue Sarcoma

Acute Graft Versus Host Disease

Wilms' Tumor

Lymphosarcoma

Neuroepithelioma

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

blood sampling before, during and after doxorubicin administration

doxorubicin

Joachim Boos, MD, Prof.

Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity .

* Paediatric patients up to the age of 17 years will be included. Number and time points of PK sampling will depend on age and tumour type.
* PK samples will be collected from two doxorubicin administrations. Analyzing samples from two doxorubicin administrations will allow distinguishing between interindividual, intraindividual and residual variability.
* Doxorubicin and its major metabolite doxorubicinol will be measured in plasma using HPLC
* In addition, the natriuretic peptide BNP and the precursors NT-pro ANP and NT-proBNP as well as troponin T will be measured in plasma up to 28 days after doxorubicin administration to evaluate their use as clinical markers for cardiotoxicity.
* A data set of max 5 samples (3 +2 (in the 1st + 2nd Doxorubicin sampling periods)) will be collected in the younger children (\< 3 years) and a data set of max. 8 samples ( 5 + 3) will be collected in the older children. Samples will be taken at predefined time points/ time intervals.
* An additional DNA sample will be taken and analyzed for genetic polymorphisms. The influence of genotype on pharmacokinetics and metabolism will be investigated by appropriate statistical methods, including population pharmacokinetic analyses. Genes to study would include MDR1 and SLC22A16, both involved in the transport of doxorubicin and AKR1A1 and CBR1, both involved in the reduction of doxorubicin to doxorubicinol. Selected genotypes will be incorporated as covariates into the population pharmacokinetic models developed. The potential impact of genetic variation will be evaluated in the context of other sources of variability such as age, weight, gender etc

Pharmacokinetic Study of Doxorubicin in Children With Cancer

Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia

Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.

Obtain one whole blood sample per patient, if separate consent was given.

Measure troponin T, troponin I, BNP, NT-proBNP, NT-proANP. Collect samples at two different doxorubicin infusions before and up to 1month after doxorubicin administration.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Remote Ischaemic Conditioning in Oncology Patients	NCT02471885	Cardiotoxicity	Remote Ischaemi... Placebo	16 Years - 80 Years	University College, London
Kinetics of Troponin and BNP in Breast Cancer Chemotherapy With Adriamycin and Trastuzumab	NCT01771549	Breast Cancer		18 Years -	Mayo Clinic
Kinetics of Troponin and BNP in Breast Cancer Chemotherapy With Adriamycin and Trastuzumab	NCT01771549	Breast Cancer		18 Years -	Mayo Clinic
Extensive CArdioVAscular Characterization and Follow-up of Patients Receiving Immune Checkpoint Inhibitors	NCT05699915	Cancer Immune-related ... Cardiac Abnorma... Immune Checkpoi... Diastolic Dysfu... Atherosclerosis Cardiotoxicity	Cardiology cons... Chest Computed ... Non-invasive en... Electrocardiogr... Extra serum sam...	18 Years -	Algemeen Ziekenhuis Maria Middelares
Pharmacokinetic Study of Doxorubicin in Children With Cancer	NCT01095926	Wilms Tumor Neuroblastoma Soft Tissue Sar... Acute Lymphobla...	doxorubicin	- 17 Years	University Hospital Muenster

Spots Global Cancer Trial Database for troponin

Every month we try and update this database with for troponin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for troponin

Every month we try and update this database with for troponin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for troponin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.