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The Impact of Using Nicorandil for the Prevention of Doxorubicin-Induced Cardiotoxicity (NICBREASTRCT)

1. november 2026 opdateret af: Noha Salah Ahmed Abdelaziz, Universiti Sains Malaysia

The Impact of Using Nicorandil for the Prevention of Doxorubicin-Induced Cardiotoxicity, Including Quality of Life and Cost Analysis Among Breast Cancer Patients at Breast Cancer Hospital: A Randomized Controlled Trial in Egypt

Breast cancer is one of the world's most common cancers in females. Most of the chemotherapy protocols used to treat breast cancer involve doxorubicin. Doxorubicin has a very significant antitumor effect on breast tumors. One of the obstacles that hinders the use of doxorubicin is cardiotoxicity. Although many agents are used to address this issue, only dexrazoxane is FDA-approved. One suggested pathway for doxorubicin-induced cardiotoxicity is due to calcium imbalance. Calcium ions are very important in controlling the heart's function. Nicorandil is an anti-anginal agent that shows cardioprotective effects against doxorubicin-induced cardiotoxicity in preclinical trials. Not only that, but preclinical studies on rats and mice have also shown that it has antitumor and augmenting effects on doxorubicin's anticancer properties. Here in our trial, the impact of the nicorandil will be assessed on breast cancer patients. The chosen method will be a parallel, open-label, randomized clinical trial. The selected sampling method will be stratified blocks based on radiotherapy and HFA-ICOS baseline scores. The sample size will be 146 patients, who will be randomized using a premuted block. The primary parameter will be the ejection fraction. The secondary parameters will include cardiac troponins, creatine kinase myocardial band, safety assessment of nicorandil use on the gastrointestinal and cardiovascular systems, quality of life after nicorandil use, cost-effectiveness and cost-utility of nicorandil, and the quality of life and baseline cardiac scoring system.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

There are different modalities for the treatment of breast cancer, including surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, and immunotherapy. Chemotherapy is important to decrease the tumor size of the breast, making breast conservation possible.

Doxorubicin (DOX) is an anticancer agent used in chemotherapy to treat hematological and solid cancers. In breast cancer, DOX is used in many protocols. One of the well-known chemotherapeutic protocols is AC-T (adriamycin, cyclophosphamide, and paclitaxel). The mechanism of DOX cytotoxicity is due to free radical formation, which is associated with DOX cardiotoxic adverse events. DOX-induced cardiomyopathy leads to fibrosis of myocardial cells that causes cardiovascular disorders. DOX-cardiotoxicity is considered irreversible (type I) cardiotoxicity. Echocardiography remains the gold standard for assessing cardiac function primarily by evaluating the left ventricular ejection fraction (LVEF). Besides, echocardiography could assess the global longitudinal strain (GLS), a measure of the left ventricle's longitudinal shortening, which is more sensitive for detecting early myocardial dysfunction that cannot be assessed by LVEF alone. Changes in GLS can indicate subclinical cardiac impairment, which is considered an early warning sign of doxorubicin-induced cardiotoxicity.

Biomarkers of cardiotoxicity are a non-invasive method for early detection in patients undergoing doxorubicin therapy. These biomarkers enable clinicians to initiate preventive treatment regimens earlier, as they indicate long-term LVEF deterioration. Studies have shown that the risk of DOX cardiotoxicity increases at a cumulative dose of 400 mg/m² without other risk factors. DOX-induced cardiotoxicity may lead to increased morbidity and mortality.

As a consequence, for most of the patients with DOX-induced cardiotoxicity, their quality of life will be affected. One of the methods used for quality of life assessment is the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) Core 30 (QLQ-C30), and another one for breast cancer patients (BR-42). A study has shown the deterioration in the psychological and physical state of breast cancer patients on chemotherapy treatment.

Many antioxidant supplements are used to treat DOX-induced cardiotoxicity. Dexrazoxane is the only FDA-approved cardioprotective agent for DOX cardiotoxicity. Although other supplements like omega-3, vitamin E, and levocarnitine have shown significant effects in preclinical studies, only a few have been investigated in clinical practice. Yet, few studies have targeted the Ca²⁺ imbalance caused by DOX administration.

Nicorandil (NIC), a nicotinamide ester with a nitrate group, is used in several medical conditions in Japan and Europe. Nicorandil's (NIC) cardioprotective effect was caused by selective activation of the mitochondrial ATP-sensitive K+ channel (mitoKATP) and nitric oxide (NO) donor activity. These will lead to cardiac muscle relaxation and decrease reactive oxygen species and cell death. They also maintain calcium homeostasis and prevent high intracellular calcium levels, which can cause cellular malfunction and apoptosis.

Available studies show promising results for NIC in patients with heart failure. Preclinical studies suggested that NIC may also have a protective effect against DOX-induced cardiotoxicity by avoiding mitochondrial dysfunction without affecting the antitumor activity of DOX. Further clinical studies are needed to confirm the protective effect of NIC against DOX-induced cardiotoxicity.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

146

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Egypten
    • Cairo Governorate
      • Cairo, Cairo Governorate, Egypten

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 65 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Kvinde

Beskrivelse

Inclusion criteria

  • 18 years - 65 years
  • Female patients with stage (I, II, III) breast cancer.
  • Left ventricular ejection fraction (LVEF) ≥ 55% upon breast cancer diagnosis.
  • Systolic blood pressure ≥ 90 mmHg
  • Estimated glomerular filtration rate (eGFR ≥ 60 mL/min per 1.73 m²). Exclusion criteria
  • Pregnant and lactating mothers.
  • Metastatic breast cancer. (stage IV).
  • Patients are currently using beta-blockers and phosphodiesterase 5 inhibitors.
  • Patients who require chronic use of aspirin or chronic use of corticosteroids (≥3 months).
  • Patients who are diagnosed with heart failure, myocardial infarction, stable angina, cardiogenic shock, hypovolemia, or previous coronary revascularization.
  • Previously treated with anthracyclines.
  • Previous gastrointestinal bleeding, ulcer, or perforation.
  • Severe hepatic impairment (ALT, AST ≥ 5 upper limit normal), or diagnosed with clinical evidence of hepatic ascites, encephalopathy, variceal bleeding, decompensated cirrhosis, and acute hepatitis.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Forebyggelse
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: STANDARD CARE

DOX protocol AC regimen (doxorubicin 60 mg/m2 intravenous every 21 days, cyclophosphamide 600 mg/m2 intravenous every 21 days for 4 cycles).
Medicin: Adriamycin (Doxorubicin)

AC regimen (doxorubicin 60 mg/m2 intravenous every 21 days, cyclophosphamide 600 mg/m2 intravenous every 21 days for 4 cycles).

Andre navne:
  • DOX
  • AC-T PROTCOL
Eksperimentel: Treatment

NIC ( 5-10 mg per day ) + DOX protcol
Medicin: Adriamycin (Doxorubicin)

AC regimen (doxorubicin 60 mg/m2 intravenous every 21 days, cyclophosphamide 600 mg/m2 intravenous every 21 days for 4 cycles).

Andre navne:
  • DOX
  • AC-T PROTCOL
Medicin: Nicorandil Oral Tablet

drug

Andre navne:
  • NIC

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
To evaluate the effect of nicorandil on left ventricular ejection fraction in breast cancer patients receiving doxorubicin.
Tidsramme: before the treatment initiation, at the 3rd and the 6th months of the treatment initiation

Elevation or maintenance of Ejection fraction percentage (EF %) using echocardiogram
before the treatment initiation, at the 3rd and the 6th months of the treatment initiation
To evaluate the safety of nicorandil
Tidsramme: before the treatment initiation, at the 3rd and the 6th months of the treatment initiation

possible hypotension (mmhg)
before the treatment initiation, at the 3rd and the 6th months of the treatment initiation

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
To assess patients' quality of life
Tidsramme: From enrollment, at the 3rd and the 6th months of the treatment

using the modified EORTC QLQ-BR42, where 100 is the best quality and 0 is the worst.
From enrollment, at the 3rd and the 6th months of the treatment
To determine the effect of nicorandil on global longitudinal strain in breast cancer patients receiving doxorubicin.
Tidsramme: From enrollment and at the 3rd and the 6th months of treatment

by using echogradiogram in %
From enrollment and at the 3rd and the 6th months of treatment
To evaluate the cost-utility of nicorandil as a cardioprotective agent against doxorubicin-induced cardiotoxicity.
Tidsramme: at the treatment initiation, the 3rd and the 6th months of the treament

using the QALY unit
at the treatment initiation, the 3rd and the 6th months of the treament
To assess the effect of nicorandil on cardiac biomarkers
Tidsramme: at the treatment initiation, at the 3rd and 6th months of the treament

by assessing, including cardiac troponin ng/ml
at the treatment initiation, at the 3rd and 6th months of the treament

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Universiti Sains Malaysia

Efterforskere

  • Ledende efterforsker: Noha S Abdelaziz, PhD, Universiti Sains Malaysia
  • Ledende efterforsker: Sabariah N H, Ass.Prof, Universiti Sains Malaysia
  • Ledende efterforsker: Ayman A G, Prof, National Cancer Institute (NCI)
  • Ledende efterforsker: Nur H Md, lecturer, Universiti Sains Malaysia

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. december 2026

Primær færdiggørelse (Anslået)

1. juni 2027

Studieafslutning (Anslået)

1. september 2027

Datoer for studieregistrering

Først indsendt

3. oktober 2026

Først indsendt, der opfyldte QC-kriterier

22. oktober 2026

Først opslået (Faktiske)

27. oktober 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

3. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

1. november 2026

Sidst verificeret

1. november 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NIC in DOX Cardiotoxicity

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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Studerer et amerikansk FDA-reguleret enhedsprodukt

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