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Doxorubicin Induced CardiotoxicityPhase 2NICBREASTRCTNCT07897409

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

A Phase 2 study testing Nicorandil Oral Tablet and Adriamycin (Doxorubicin) in people with Doxorubicin Induced Cardiotoxicity and Doxorubicin Induced Cardiomyopathy, run by Universiti Sains Malaysia at 1 site in Egypt.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 years, women only
What is being tested?
Nicorandil Oral Tablet and Adriamycin (Doxorubicin)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
146 participants
Where
1 siteEgypt
Study dates
1 Dec 2026to 1 Sep 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 13Show fewer
  • 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.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Egypt1 site
  • National Cancer Institute

    Cairo, Cairo Governorate

    Noha S Abdelaziz, Phd, 00201012305323, nohasalahphr.ct@gmail.com

Other trials in Egypt

About this study

Official title: 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.

Read the detailed description

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.

Being tested
Nicorandil Oral Tablet, Adriamycin (Doxorubicin)
Keywords
doxorubicin, cardiomyopathy, cardiotoxicity, nicorandil
Medical subject headings
Cardiomyopathies, Cardiotoxicity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nicorandil Oral TabletDrug

    Also called NIC

    drug

  • Adriamycin (Doxorubicin)Drug

    Also called DOX, AC-T PROTCOL

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

Study groups in NCT07897409
Study groupRoleWhat they receive
STANDARD CAREActive comparatorDOX protocol AC regimen (doxorubicin 60 mg/m2 intravenous every 21 days, cyclophosphamide 600 mg/m2 intravenous every 21 days for 4 cycles).
Receives: Drug: Adriamycin (Doxorubicin)
TreatmentExperimentalNIC ( 5-10 mg per day ) + DOX protcol
Receives: Drug: Nicorandil Oral Tablet; Drug: Adriamycin (Doxorubicin)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To evaluate the effect of nicorandil on left ventricular ejection fraction in breast cancer patients receiving doxorubicin.

    Elevation or maintenance of Ejection fraction percentage (EF %) using echocardiogram

    Measured: before the treatment initiation, at the 3rd and the 6th months of the treatment initiation

  2. To evaluate the safety of nicorandil

    possible hypotension (mmhg)

    Measured: before the treatment initiation, at the 3rd and the 6th months of the treatment initiation

Secondary outcomes (4)
  1. To assess patients' quality of life

    using the modified EORTC QLQ-BR42, where 100 is the best quality and 0 is the worst.

    Measured: From enrollment, at the 3rd and the 6th months of the treatment

  2. To determine the effect of nicorandil on global longitudinal strain in breast cancer patients receiving doxorubicin.

    by using echogradiogram in %

    Measured: From enrollment and at the 3rd and the 6th months of treatment

  3. To evaluate the cost-utility of nicorandil as a cardioprotective agent against doxorubicin-induced cardiotoxicity.

    using the QALY unit

    Measured: at the treatment initiation, the 3rd and the 6th months of the treament

  4. To assess the effect of nicorandil on cardiac biomarkers

    by assessing, including cardiac troponin ng/ml

    Measured: at the treatment initiation, at the 3rd and 6th months of the treament

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2026
  2. Study start1 Dec 2026 (estimated)
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion1 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
146 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07897409
Sponsor's protocol ID
NIC in DOX Cardiotoxicity
Acronym
NICBREASTRCT
Status last verified
Nov 2026
First submitted
3 Oct 2026
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H. Cancer incidence in egypt: results of the national population-based cancer registry program. J Cancer Epidemiol. 2014;2014:437971. doi: 10.1155/2014/437971. Epub 2014 Sep 21.

    PubMed 25328522
  • References: 2. Cuthrell KM, Tzenios N. Breast Cancer: Updated and Deep Insights. International Research Journal of Oncology. 2023;6(1):104-18.

  • Obeagu EI, Obeagu GU. Breast cancer: A review of risk factors and diagnosis. Medicine (Baltimore). 2024 Jan 19;103(3):e36905. doi: 10.1097/MD.0000000000036905.

    PubMed 38241592

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nicorandil Oral Tablet and Adriamycin (Doxorubicin) in people with Doxorubicin Induced Cardiotoxicity and Doxorubicin Induced Cardiomyopathy, run by Universiti Sains Malaysia at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Noha S A, Phd (00201012305323, nohasalahphr.ct@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the effect of nicorandil on left ventricular ejection fraction in breast cancer patients receiving doxorubicin. (time frame: before the treatment initiation, at the 3rd and the 6th months of the treatment initiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07897409, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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