Colchicine Versus Beta-blockers, Angiotensin-converting Enzyme Inhibitors, and Statins for Prevention of Chemotherapy-Induced Cardiomyopathy

NCT06304896 | Not Yet Recruiting Phase 1

• 1 other identifier: #18240343
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

BASiC-CIC Trial is a multicenter, double-blinded, randomized, placebo-controlled clinical trial to investigate whether repurposing colchicine or a combination of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins will be effective as a prophylactic treatment for the prevention of chemotherapy-induced cardiomyopathy, reduction of major adverse cardiovascular events, and all-cause mortality.

Conditions

Chemotherapy Induced Systolic Dysfunction

Outcome Measures

Primary Outcomes (2)

• Chemotherapy-induced cardiomyopathy

  An identification of a drop in the LVEF using echocardiography more than or equal to 10% from the baseline at the time of presentation and/or a decline of the LVEF less than 50%.

  6 months

• Chemotherapy-induced cardiomyopathy

  An identification of at least one value of serum NT-proBNP over 125 pg/mL in patients less than 75 years of age, or 450pg/mL in patients more than 75 years of age.

  6 months

Secondary Outcomes (2)

• Major Adverse Cardiovascular Events

  6 months

• All-Cause Mortality

  6 months

Study Arms (3)

The Cardioprotective Group (CPG)

ACTIVE COMPARATOR

50 patients will receive a low-dose Beta-blockers in the form of Carvedilol 6.25 mg PO twice daily, a low-dose ACE inhibitors in the form of Ramipril 2.5 mg PO once daily, and a statin in the form of rosuvastatin 20 mg oral tablets.

Drug: Carvedilol; Drug: Ramipril; Drug: Rosuvastatin

The Immunomodulatory Group (IMG)

ACTIVE COMPARATOR

50 patients will receive Colchicine 0.6 PO once daily.

Drug: Colchicine

The Placebo Control Group (PCG)

PLACEBO COMPARATOR

50 patients will receive a placebo as a control group.

Drug: Placebo

Interventions

Carvedilol DRUG

Carvedilol 6.25 mg oral tablets. Prescribed: Twice daily PO with 200 mL of water.

Also known as: Carvid, Coreg

The Cardioprotective Group (CPG)

Ramipril DRUG

Ramipril 2.5 mg oral capsules. Prescribed: Once daily PO with 200 mL of water.

Also known as: Tritace, Altace

The Cardioprotective Group (CPG)

Rosuvastatin DRUG

Rosuvastatin 20 mg oral tablets. Prescribed: Once daily PO with 200 mL of water.

Also known as: Crestor

The Cardioprotective Group (CPG)

Colchicine DRUG

Colchicine 0.6 mg oral tablets/capsules. Prescribed: Once daily PO with 200 mL of water.

Also known as: Colcrys, Mitigare

The Immunomodulatory Group (IMG)

Placebo DRUG

Placebo oral capsules. Prescribed: Once daily PO with 200 mL of water.

The Placebo Control Group (PCG)

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent prior to performing study procedures.
• A cancer patient who is a candidate for a guideline-directed, anthracycline-based chemotherapy with or without the anti-HER2 trastuzumab.
• Baseline LVEF ≥ 50% without evident structural heart disease by pre-treatment echocardiographic examination.

You may not qualify if:

• Critically ill Cancer patients who are admitted to ICU.
• Ischemic cardiomyopathy with LVEF ≤ 50%.
• Dilated cardiomyopathy with LVEF ≤ 50%.
• Advanced valvular heart disease (severe valvular affection in the form of stenosis or regurgitation).
• Systolic BP \< 90 mmHg or diastolic BP \< 60 mmHg.
• Liver cell failure.
• End-stage chronic kidney disease on regular dialysis.
• Pregnancy.
• Lactation.
• Chronic muscle diseases such as dermatomyositis, polymyositis, or muscular dystrophy.
• Acute trauma or burns within 2 weeks.
• History of allergy to the implemented drugs.

Sponsors & Collaborators

• Arab Contractors Medical Centre: lead

Study Sites (1)

Arab Contractors Medical Centre

Cairo, Egypt

Location

Related Publications (20)

• Sun X, Duan J, Gong C, Feng Y, Hu J, Gu R, Xu B. Colchicine Ameliorates Dilated Cardiomyopathy Via SIRT2-Mediated Suppression of NLRP3 Inflammasome Activation. J Am Heart Assoc. 2022 Jul 5;11(13):e025266. doi: 10.1161/JAHA.122.025266. Epub 2022 Jun 29.

  PMID: 35766262 BACKGROUND

• Zhang FS, He QZ, Qin CH, Little PJ, Weng JP, Xu SW. Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review. Acta Pharmacol Sin. 2022 Sep;43(9):2173-2190. doi: 10.1038/s41401-021-00835-w. Epub 2022 Jan 19.

  PMID: 35046517 BACKGROUND

• Kuo MC, Chang SJ, Hsieh MC. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients: A 12-Year Cohort Study. Medicine (Baltimore). 2015 Dec;94(50):e1570. doi: 10.1097/MD.0000000000001570.

  PMID: 26683907 BACKGROUND

• Zhang T, Chen W, Jiang X, Liu L, Wei K, Du H, Wang H, Li J. Anticancer effects and underlying mechanism of Colchicine on human gastric cancer cell lines in vitro and in vivo. Biosci Rep. 2019 Jan 15;39(1):BSR20181802. doi: 10.1042/BSR20181802. Print 2019 Jan 31.

  PMID: 30429232 BACKGROUND

• Authors/Task Force Members:; McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022 Jan;24(1):4-131. doi: 10.1002/ejhf.2333.

  PMID: 35083827 BACKGROUND

• Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.

  PMID: 35363499 BACKGROUND

• Bosch X, Rovira M, Sitges M, Domenech A, Ortiz-Perez JT, de Caralt TM, Morales-Ruiz M, Perea RJ, Monzo M, Esteve J. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013 Jun 11;61(23):2355-62. doi: 10.1016/j.jacc.2013.02.072. Epub 2013 Apr 10.

  PMID: 23583763 BACKGROUND

• Golwala H. Enalapril/carvedilol for prevention of chemotherapy-induced heart failure: an end to the problem. J Am Coll Cardiol. 2013 Dec 24;62(25):2450-2451. doi: 10.1016/j.jacc.2013.06.059. Epub 2013 Sep 4. No abstract available.

  PMID: 24013049 BACKGROUND

• Spallarossa P, Guerrini M, Arboscello E, Sicbaldi V. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction. J Am Coll Cardiol. 2013 Dec 24;62(25):2451-2452. doi: 10.1016/j.jacc.2013.07.077. Epub 2013 Sep 4. No abstract available.

  PMID: 24013048 BACKGROUND

• Smiseth OA, Edvardsen T, Skulstad H. Cardioprotection during chemotherapy: need for faster transfer of knowledge from cardiology to oncology and role for a cardio-oncologist. J Am Coll Cardiol. 2013 Jun 11;61(23):2363-4. doi: 10.1016/j.jacc.2013.02.073. Epub 2013 Apr 10. No abstract available.

  PMID: 23583243 BACKGROUND

• Guglin M, Krischer J, Tamura R, Fink A, Bello-Matricaria L, McCaskill-Stevens W, Munster PN. Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer. J Am Coll Cardiol. 2019 Jun 11;73(22):2859-2868. doi: 10.1016/j.jacc.2019.03.495.

  PMID: 31171092 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

• Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, Inanc T, Oguzhan A, Eryol NK, Topsakal R, Ergin A. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006 Dec 5;48(11):2258-62. doi: 10.1016/j.jacc.2006.07.052. Epub 2006 Nov 9.

  PMID: 17161256 BACKGROUND

• Shah P, Garris R, Abboud R, Vasudev R, Patel H, Doshi R, Shamoon F, Bikkina M. Meta-Analysis Comparing Usefulness of Beta Blockers to Preserve Left Ventricular Function During Anthracycline Therapy. Am J Cardiol. 2019 Sep 1;124(5):789-794. doi: 10.1016/j.amjcard.2019.05.046. Epub 2019 Jun 6.

  PMID: 31307662 BACKGROUND

• Wittayanukorn S, Qian J, Westrick SC, Billor N, Johnson B, Hansen RA. Prevention of Trastuzumab and Anthracycline-induced Cardiotoxicity Using Angiotensin-converting Enzyme Inhibitors or beta-blockers in Older Adults With Breast Cancer. Am J Clin Oncol. 2018 Sep;41(9):909-918. doi: 10.1097/COC.0000000000000389.

  PMID: 28537988 BACKGROUND

• Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL; LoDoCo2 Trial Investigators. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020 Nov 5;383(19):1838-1847. doi: 10.1056/NEJMoa2021372. Epub 2020 Aug 31.

  PMID: 32865380 BACKGROUND

• Deftereos S, Giannopoulos G, Panagopoulou V, Bouras G, Raisakis K, Kossyvakis C, Karageorgiou S, Papadimitriou C, Vastaki M, Kaoukis A, Angelidis C, Pagoni S, Pyrgakis V, Alexopoulos D, Manolis AS, Stefanadis C, Cleman MW. Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study. JACC Heart Fail. 2014 Apr;2(2):131-7. doi: 10.1016/j.jchf.2013.11.006.

  PMID: 24720919 BACKGROUND

• Rogers JK, Jhund PS, Perez AC, Bohm M, Cleland JG, Gullestad L, Kjekshus J, van Veldhuisen DJ, Wikstrand J, Wedel H, McMurray JJ, Pocock SJ. Effect of rosuvastatin on repeat heart failure hospitalizations: the CORONA Trial (Controlled Rosuvastatin Multinational Trial in Heart Failure). JACC Heart Fail. 2014 Jun;2(3):289-97. doi: 10.1016/j.jchf.2013.12.007. Epub 2014 Apr 30.

  PMID: 24952697 BACKGROUND

• Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G; Gissi-HF Investigators. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Oct 4;372(9645):1231-9. doi: 10.1016/S0140-6736(08)61240-4. Epub 2008 Aug 29.

  PMID: 18757089 BACKGROUND

• van der Harst P, de Boer RA. Statins in the treatment of heart failure. Circ Heart Fail. 2010 May;3(3):462-4. doi: 10.1161/CIRCHEARTFAILURE.110.956342. No abstract available.

  PMID: 20484198 BACKGROUND

MeSH Terms

Interventions

Carvedilol; Ramipril; Rosuvastatin Calcium; Colchicine

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Alkaloids

Study Officials

• Eslam Abbas, MBChB, MSc

  Arab Contractors Medical Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eslam Abbas, MBChB, MSc

CONTACT

01023054574; islam.omr@med.au.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 12, 2024
• Study Start: May 1, 2024
• Primary Completion: May 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

EG (1)