The Impact of Using Nicorandil for the Prevention of Doxorubicin-Induced Cardiotoxicity (NICBREASTRCT)
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.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
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.
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- フェーズ2
連絡先と場所
研究連絡先
研究連絡先
- 名前：Noha S A, Phd
- 電話番号：00201012305323
- メール：nohasalahphr.ct@gmail.com
研究場所
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Cairo Governorate
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Cairo、Cairo Governorate、エジプト
- National Cancer Institute
-
コンタクト：
- Noha S Abdelaziz, Phd
- 電話番号：00201012305323
- メール：nohasalahphr.ct@gmail.com
-
-
参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
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アクティブコンパレータ：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). |
AC regimen (doxorubicin 60 mg/m2 intravenous every 21 days, cyclophosphamide 600 mg/m2 intravenous every 21 days for 4 cycles).
他の名前：
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|
実験的：Treatment
NIC ( 5-10 mg per day ) + DOX protcol |
AC regimen (doxorubicin 60 mg/m2 intravenous every 21 days, cyclophosphamide 600 mg/m2 intravenous every 21 days for 4 cycles).
他の名前：
drug
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
To evaluate the effect of nicorandil on left ventricular ejection fraction in breast cancer patients receiving doxorubicin.
時間枠：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
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To evaluate the safety of nicorandil
時間枠：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
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
To assess patients' quality of life
時間枠：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
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To determine the effect of nicorandil on global longitudinal strain in breast cancer patients receiving doxorubicin.
時間枠：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.
時間枠：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
|
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To assess the effect of nicorandil on cardiac biomarkers
時間枠：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
|
協力者と研究者
捜査官
捜査官
- 主任研究者：Noha S Abdelaziz, PhD、Universiti Sains Malaysia
- 主任研究者：Sabariah N H, Ass.Prof、Universiti Sains Malaysia
- 主任研究者：Ayman A G, Prof、National Cancer Institute (NCI)
- 主任研究者：Nur H Md, lecturer、Universiti Sains Malaysia
出版物と役立つリンク
一般刊行物
- 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.
- 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.
研究記録日
主要日程の研究
研究開始 (推定)
研究開始
一次修了 (推定)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
その他の研究ID番号
- NIC in DOX Cardiotoxicity
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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