[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100474986":3},{"organization":4,"armGroups":7,"interventions":20,"overallOfficials":30,"centralContacts":35,"locations":45,"responsibleParty":105,"collaborators":107,"id":111,"slug":112,"hasResults":113,"nctId":114,"briefTitle":115,"officialTitle":116,"acronym":26,"eligibilityCriteria":117,"healthyVolunteers":113,"sex":118,"minAge":119,"maxAge":26,"enrollmentInfo":120,"targetDuration":26,"studyType":123,"phases":124,"briefSummary":126,"conditions":127,"keywords":141,"overallStatus":48,"whyStopped":26,"lastUpdateSubmitDate":150,"lastUpdatePostDateStruct":151,"startDateStruct":154,"completionDateStruct":156,"leadSponsor":158,"locationsCount":159},{"fullName":5,"class":6},"Silesian Centre for Heart Diseases","OTHER",[8,14],{"label":9,"type":10,"description":11,"interventionNames":12},"Experimental: Sacubitril\u002FValsartan","EXPERIMENTAL","After assessment of the tolerance of the drug during the single-blind period, during the which the starting dose of the drug of 100 mg b.i.d. should be increased after two weeks to the target dose 200 mg b.i.d, the patients will be randomized in 1:1 ratio to either intervention or placebo group. In the experimental arm, the patients after randomization will receive the dose 200 mg b.i.d of sacubitril\u002Fvalsartan for the course of the study. If the patients does not tolerate the target dose of 200 mg b.i.d., the reduction of the drug dose to 100 mg b.i.d. will be possible at the discretion of the physician-in-charge.",[13],"Drug: Sacubitril-valsartan",{"label":15,"type":16,"description":17,"interventionNames":18},"Placebo","PLACEBO_COMPARATOR","After assessment of the tolerance of the drug during the single-blind period, during the which the starting dose of the drug of 100 mg b.i.d. should be increased after two weeks to the target dose 200 mg b.i.d, the patients will be randomized in 1:1 ratio to either intervention or placebo group. In the placebo arm, the patients will receive the matching placebo with an identical strategy of dose reduction as in the intervention group, at the discretion of the physician-in-charge.",[19],"Drug: Placebo",[21,27],{"type":22,"name":23,"description":24,"armGroupLabels":25,"otherNames":26},"DRUG","Sacubitril-valsartan","Sacubitril\u002Fvalsartan (Entresto®) administered in the target dose of 200 mg b.i.d. (97\u002F103 mg of sacubitril and valsartan respectively) for the period of 24 months. In case of target dose intolerance, the physician-in-charge will be able to reduce the dose to 100 mg b.i.d. (49\u002F51mg of sacubitril and valsartan respectively). Physicians will be strongly encouraged to evaluate the possibility of drug dose uptitration to the target dose of 200 mg b.i.d.",[9],null,{"type":22,"name":15,"description":28,"armGroupLabels":29,"otherNames":26},"Placebo matching the sacubitril\u002Fvalsartan (Entresto®) administered in the target dose matching the dosing of 200 mg b.i.d. (97\u002F103 mg) for the period of 24 months. In case of intolerance of target dose of placebo, the physician-in-charge will be able to reduce the dose to placebo matching the dose of 100 mg b.i.d. (49\u002F51mg). Physicians will be strongly encouraged to evaluate the possibility of drug dose uptitration to the target dose of placebo matching the dose of 200 mg b.i.d.",[15],[31],{"name":32,"affiliation":33,"role":34},"Mateusz Tajstra","3rd Department of Cardiology, School of Medical Sciences in Zabrze, Medical University of Silesia, Katowice; Silesian Center for Heart Diseases","PRINCIPAL_INVESTIGATOR",[36,41],{"name":37,"role":38,"phone":39,"phoneExt":26,"email":40},"Mateusz Tajstra, MD, PhD, Assoc Prof","CONTACT","+48323733860","mateusztajstra@wp.pl",{"name":42,"role":38,"phone":43,"phoneExt":26,"email":44},"Lucyna Broja","+48323733853","l.broja@sccs.pl",[46,65,80,90],{"facility":47,"status":48,"city":49,"state":50,"zip":51,"country":52,"countryCode":53,"cosmosGeoPoint":54,"geoPoint":59,"contacts":60},"Regional Cancer Centre in Opole","RECRUITING","Opole","Opole Voivodeship","45-061","Poland","PL",{"type":55,"coordinates":56},"Point",[57,58],17.92604,50.67119,{"lat":58,"lon":57},[61],{"name":62,"role":38,"phone":63,"phoneExt":26,"email":64},"Barbara Radecka, MD, PhD","+48774416001","brad@onkologia.opole.pl",{"facility":66,"status":48,"city":67,"state":68,"zip":69,"country":52,"countryCode":53,"cosmosGeoPoint":70,"geoPoint":74,"contacts":75},"Maria Sklodowska-Curie Institute - Oncology Centre (MSCI), Gliwice Branch","Gliwice","Silesian Voivodeship","44102",{"type":55,"coordinates":71},[72,73],18.67658,50.29761,{"lat":73,"lon":72},[76],{"name":77,"role":38,"phone":78,"phoneExt":26,"email":79},"Michal Jarząb, MD, PhD, Associate Professor","+48322788886","onkologia@io.gliwice.pl",{"facility":81,"status":82,"city":83,"state":68,"zip":84,"country":52,"countryCode":53,"cosmosGeoPoint":85,"geoPoint":89,"contacts":26},"Silesian Center for Heart Diseases","ACTIVE_NOT_RECRUITING","Zabrze","41800",{"type":55,"coordinates":86},[87,88],18.78576,50.32492,{"lat":88,"lon":87},{"facility":91,"status":48,"city":92,"state":93,"zip":94,"country":52,"countryCode":53,"cosmosGeoPoint":95,"geoPoint":99,"contacts":100},"Holy Cross Cancer Centre, Cardio-Oncology Division","Kielce","Świętokrzyskie Voivodeship","25-734",{"type":55,"coordinates":96},[97,98],20.62752,50.87033,{"lat":98,"lon":97},[101],{"name":102,"role":38,"phone":103,"phoneExt":26,"email":104},"Barbara Sosnowska-Pasiarska, MD, PhD","+48 41 34 56 882","repikus@poczta.onet.pl",{"type":106,"investigatorFullName":26,"investigatorTitle":26,"investigatorAffiliation":26,"oldNameTitle":26,"oldOrganization":26},"SPONSOR",[108],{"name":109,"class":110},"Medical Research Agency, Poland","OTHER_GOV","100474986","phase-4-sacubitrilvalsartan-in-primary-prevention-of-the-cardiotoxicity-of-systematic-breast-cancer-treatment-mainstream-100474986",false,"NCT05465031","Sacubitril\u002FValsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)","Sacubitril\u002FValsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent","Inclusion Criteria:\n\n* Written informed consent\n* Female gender, aged 18 years and over\n* Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (Estrogen receptor - ER, Progesterone receptor - PR, Human epidermal growth factor receptor 2 - HER2, Kiel - Ki67)\n* Ability to take oral medication and willingness to adhere to the planned regimen\n* Tumor grade IA-IIIC or oligometastatic grade IV\n* Radical treatment plan including surgery\n* Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and\u002For anti-HER2 drugs\n* Eastern Cooperative Oncology Group (ECOG) 0-2 general status\n* LVEF ≥ 50% as assessed by echocardiography\n* Sinus rhythm\n\nExclusion Criteria:\n\n* Prior anthracycline-based chemotherapy and\u002For thoracic radiotherapy (prior to diagnosis of the cancer being the present cause of therapy)\n* Clinically relevant HF (NYHA II-IV)\n* Myocardial infarction (MI) within the last \\\u003C 3 months\n* Symptomatic hypotension or systolic blood pressure (SBP) \\\u003C 90 mmHg\n* Significant valvular disease, symptomatic coronary artery disease (CCS\\>2), significant atrioventricular (AV) block, symptomatic sinus node dysfunction\n* Expected survival \\\u003C12 months\n* Glomerular filtration rate (GFR) \\\u003C30 ml\u002Fmin\u002F1.73 m2 (screening visit)\n* K+\\>5.5mmol\u002FL (screening visit)\n* Contraindications to angiotensin converting enzyme inhibitor (ACE-I)\u002Fangiotensin II receptor blocker (ARB) or LCZ696 if not listed among criteria\n* Active untreated liver disease\n* Pregnancy\n* Conditions\u002Fcircumstances that may lead to non-compliance with medical staff recommendations (e.g. active drug\u002Falcohol dependence, poorly controlled mental illness)","FEMALE","18 Years",{"count":121,"type":122},600,"ESTIMATED","INTERVENTIONAL",[125],"PHASE4","Breast cancer is the most commonly cancer in women in the overall global population. According to the World Cancer Research Fund International, there were more than 2.25 million new cases of breast cancer in women in 2020. Although the modern treatment strategies, based on the complex care, which consists of surgery, radiotherapy, hormone therapy, and targeted chemotherapy directed at specific cancer molecules have substantially reduced the risk of death due to breast cancer, their wide adoption results in the wider prevalence of cardiotoxicity, defined as either symptomatic heart failure, or asymptomatic contractile dysfunction. The occurrence of cardiotoxicity induced by anti-cancer therapies is estimated at 5-15%, and its development is the primary cause of therapy termination, which significantly reduces the probability of the efficacy of treatment. Several attempts have been made to determine the efficacious preventive strategy, which could diminish the risk of cancer-therapy induced cardiotoxicity. The results of the prior studies indicated a trend towards lower risk of troponin elevation, or left ventricular contractile dysfunction with the introduction of drugs interfering with the renin-angiotensin-aldosterone (RAA) axis, which constitute the primary treatment modality in heart failure with reduced ejection fraction (HFrEF). Sacubitril\u002Fvalsartan, the novel therapeutic agent, has been demonstrated to significantly improve prognosis in patients with HFrEF. Prior retrospective, small, single-center studies have shown that treatment with sacubitril\u002Fvalsartan may reduce the risk of cancer-therapy induced cardiotoxicity, or reverse contractile dysfunction caused by anti-cancer therapy. However, no large randomized data confirmed these findings.\n\nTherefore, the Sacubitril\u002FValsartan in PriMAry preventIoN of the cardiotoxicity of systematic breaST canceR trEAtMent) study, has been designed to verify, whether the preventive use of sacubitril\u002Fvalsartan administered in the doses recommended in patients with HFrEF in breast cancer patients undergoing adjuvant chemotherapy with anthracyclines or anthracyclines and HER-2 monoclonal antibodies, will reduce the incidence of cardiotoxicity defined as impaired left ventricular systolic function on transthoracic echocardiography (TTE). In the trial, a total of 480 patients with histologically confirmed breast cancer, who are eligible for chemotherapy with anthracyclines or anthracyclines and HER-2 monoclonal antibodies, will undergo 1:1 randomization to either preventive treatment with sacubitril\u002Fvalsartan or placebo. The patients will be followed for 24 months, and will have repetitive efficacy and safety examinations, including echocardiography, MRI (optionally), electrocardiography including 24-h Holter monitoring, blood tests, functional capacity tests and quality of life assessment.",[128,129,130,131,132,133,134,135,136,137,138,139,140],"Breast Cancer","Neoplasm, Breast","Breast Diseases","Antihypertensive Agents","Sacubitril\u002FValsartan","Angiotensin II Type 1 Receptor Blockers","Angiotensin Receptor Antagonists","Molecular Mechanisms of Pharmacological Action","Heart Failure","Cardiac Toxicity","Cancer, Therapy-Related","Cancer Therapy-Related Cardiac Dysfunction","Cardiotoxicity",[142,132,143,144,145,128,140,146,147,148,149],"LCZ696","Magnetic Resonance Imaging","Echocardiography","Cardio-oncology","Anthracyclines","Trastuzumab","Heart failure","Cardioprotection","2025-03-11",{"date":152,"type":153},"2025-03-14","ACTUAL",{"date":155,"type":153},"2024-04-17",{"date":157,"type":122},"2029-02",{"name":5,"class":6},4]