Prophylactic Lisinopril to Prevent Anthracycline Cardiomyopathy.

NCT03392740 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: GHIGHCI2018
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The intent of the study is to show the potential benefits of angiotensin converting enzyme inhibitors in preventing anthracycline induced cardiotoxicity. This is a prospective, randomized, blinded and placebo-controlled clinical trial that will enroll patients who are to be treated with anthracycline chemotherapy (doxorubicin, epirubicin, idrarubicin, or mitoxantone) to either lisinopril or placebo group. The study will be performed at the Genesys Hurley Cancer Institute. The treating oncologist who intends to start the patient on anthracycline chemotherapeutic agent will provide the patient with a recruitment flyer and informed consent form and then referred to the research nurse. Subjects interested in participation, that do not meet any of the exclusion criteria, will be consented and enrolled by the research nurse prior to their first treatment with chemotherapy. Over a period of 1 to 3 weeks the study medication will be titrated in a stepwise fashion to a target of 20 mg daily, maintaining a systolic blood pressure greater than 90 mmHg. A baseline echocardiogram with strain and strain rate imaging will be obtained prior to initiation of anthracycline chemotherapy. Subsequent echocardiograms with strain and strain rate imaging will be performed every 3 months for a total of 12 months. Patients will be followed for a total of 12 months, starting on the day of enrollment. We intend to recruit a total of 200 patients. The primary endpoint of this study is a change in change in strain and strain rate parameters prior to, during, and after anthracycline chemotherapy compared to placebo. Study data will be collected and managed using the Ascension installation of REDCap (Research Electronic Data Capture). REDCap is a secure, web application designed to support data capture for research studies, providing user-friendly web-based case report forms, real-time data entry validation (e.g. for data types and range checks), audit trails and a de-identified data export mechanism to common statistical packages. Echocardiographic data will be stored in cine-loop format on a private, password protected echocardiogram viewing software and analyzed by a separate blinded cardiologist. Patients will be evaluated according to the standard oncologic evaluation. The treating oncologist will make decisions on their treatment based on their personal standards and clinical judgement.

Conditions

Cardiomyopathy Due to Drug; Heart Failure, Systolic

Outcome Measures

Primary Outcomes (1)

• Change in strain rate from baseline

  The primary outcome is a change in strain and strain rate from baseline echocardiogram

  12 months from enrollment

Secondary Outcomes (1)

• Heart failure and left ventricular dysfunction

  12 months from enrollment

Study Arms (2)

Lisinopril treatment

EXPERIMENTAL

These patients will be initiated at 5mg lisinopril daily by the research nurse at the time of enrollment. The drug will then be titrated up by the research nurse in a stepwise fashion from 5mg, to 10mg, and then to 20mg once a day every 1 to 3 weeks according to their regular/scheduled next office visits. Blood pressure will be monitored at every visit by the research nurse if it is less than or equal to 90 mmHg

Drug: Lisinopril

Placebo Oral Tablet

PLACEBO COMPARATOR

These patients will be started on the placebo medication at the time of enrollment. According to their regular scheduled visits every 1 to 3 weeks, they will meet with the research nurse and be given a new placebo medication to take once a day.

Drug: Placebo Oral Tablet

Interventions

Lisinopril DRUG

Patients will be given lisinopril once a day prior to starting an anthracycline chemotherapy regimen and titrated up in a stepwise fashion, as allowed by patients blood pressure, to a target dose of 20mg daily.

Lisinopril treatment

Placebo Oral Tablet DRUG

Patients will be given a look-alike placebo medication once a day prior to starting an anthracycline chemotherapy regimen. They will be given a new placebo medication in a step-wise fashion over period of 1 to 3 weeks.

Placebo Oral Tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with a type of cancer and intended to be on an anthracycline chemotherapy regimen by treating oncologist.

You may not qualify if:

• Inability or unwillingness to give informed consent
• Subjects with a contraindication to angiotensin converting enzyme inhibitors such as history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme inhibitor
• Subjects with a history of hereditary or idiopathic angioedema
• Subjects currently taking aliskiren (major drug interaction-)
• Subjects currently taking a neprilysin inhibitor (e.g. sacubitril or entresto)
• Subjects already on treatment with angiotensin converting enzyme inhibitors, or taking lithium
• Renal insufficiency defined as creatinine clearance \<30
• Women \<50 who capable of child bearing who have not had surgical contraception such as hysterectomy or tubal ligation
• Oncologic life expectancy shorter than 12 months
• Systolic blood pressure \<90 mmHg prior to enrollment

Sponsors & Collaborators

• Ascension Health: lead

Study Sites (1)

Genesys Regional Medical Center

Grand Blanc, Michigan, 48439, United States

Location

Related Publications (10)

• McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracycline Chemotherapy and Cardiotoxicity. Cardiovasc Drugs Ther. 2017 Feb;31(1):63-75. doi: 10.1007/s10557-016-6711-0.

  PMID: 28185035 BACKGROUND

• Bird BR, Swain SM. Cardiac toxicity in breast cancer survivors: review of potential cardiac problems. Clin Cancer Res. 2008 Jan 1;14(1):14-24. doi: 10.1158/1078-0432.CCR-07-1033.

  PMID: 18172247 BACKGROUND

• Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, Rubino M, Veglia F, Fiorentini C, Cipolla CM. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010 Jan 19;55(3):213-20. doi: 10.1016/j.jacc.2009.03.095.

  PMID: 20117401 BACKGROUND

• Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, Durand JB, Gibbs H, Zafarmand AA, Ewer MS. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004 Jun 29;109(25):3122-31. doi: 10.1161/01.CIR.0000133187.74800.B9.

  PMID: 15226229 BACKGROUND

• Seicean S, Seicean A, Plana JC, Budd GT, Marwick TH. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. J Am Coll Cardiol. 2012 Dec 11;60(23):2384-90. doi: 10.1016/j.jacc.2012.07.067. Epub 2012 Nov 7.

  PMID: 23141499 BACKGROUND

• Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, Gravdehaug B, von Knobelsdorff-Brenkenhoff F, Bratland A, Storas TH, Hagve TA, Rosjo H, Steine K, Geisler J, Omland T. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016 Jun 1;37(21):1671-80. doi: 10.1093/eurheartj/ehw022. Epub 2016 Feb 21.

  PMID: 26903532 BACKGROUND

• Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Ryden L, Thygesen K, Uretsky BF. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation. 1999 Dec 7;100(23):2312-8. doi: 10.1161/01.cir.100.23.2312.

  PMID: 10587334 BACKGROUND

• Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017 Aug 8;70(6):776-803. doi: 10.1016/j.jacc.2017.04.025. Epub 2017 Apr 28. No abstract available.

  PMID: 28461007 BACKGROUND

• Geisberg CA, Sawyer DB. Mechanisms of anthracycline cardiotoxicity and strategies to decrease cardiac damage. Curr Hypertens Rep. 2010 Dec;12(6):404-10. doi: 10.1007/s11906-010-0146-y.

  PMID: 20842465 BACKGROUND

• Georgakopoulos P, Roussou P, Matsakas E, Karavidas A, Anagnostopoulos N, Marinakis T, Galanopoulos A, Georgiakodis F, Zimeras S, Kyriakidis M, Ahimastos A. Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Am J Hematol. 2010 Nov;85(11):894-6. doi: 10.1002/ajh.21840.

  PMID: 20872550 BACKGROUND

MeSH Terms

Conditions

Heart Failure, Systolic

Interventions

Lisinopril

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Andrew Hinojos, DO

  Genesys Regional Medical Center Department of Education

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiology Fellow

Model Details: Prospective, 1:1 randomized, double-blinded and placebo-controlled clinical trial we plan to enroll patients who are to be treated with anthracycline chemotherapy to either lisinopril or placebo group.

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 8, 2018
• Study Start: March 15, 2018
• Primary Completion: December 15, 2018
• Study Completion: December 15, 2018
• Last Updated: May 20, 2024

Record last verified: 2024-05

Locations

US (1)