Dexrazoxane for Preventing Heart Failure

(PHOENIX1 Trial)

Overseen By Edward TH Yeh, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Arkansas

Disqualifiers: Pregnancy, Cardiac disease, Renal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if Dexrazoxane can protect the heart from damage caused by the cancer drug Doxorubicin. Dexrazoxane is a heart-protecting agent approved to reduce heart damage from Doxorubicin. Volunteers will receive one dose of Dexrazoxane. The study will measure how well the drug breaks down a specific protein in the blood that might be linked to heart damage.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications.

Is dexrazoxane safe for humans?

Dexrazoxane is generally considered safe for humans and is used to protect the heart from damage caused by certain cancer treatments. Studies have shown it does not increase the risk of secondary cancers in children with acute lymphoblastic leukemia and helps prevent heart problems in adults undergoing chemotherapy. ^{1 2 3 4 5}

How does the drug Dexrazoxane differ from other heart failure treatments?

Dexrazoxane is unique because it is primarily used to protect the heart from damage caused by certain cancer treatments, rather than directly treating heart failure itself. This makes it different from other heart failure drugs that focus on improving heart function or reducing symptoms. ^{6 7 8 9 10}

Research Team

Hui-Ming Chang, MD,MPH

Principal Investigator

University of Arkansas

Eligibility Criteria

This trial is for healthy women aged 18-65 who are not pregnant, not breastfeeding, and have no current illnesses. It's not open to those with a history of kidney or heart disease, or who are currently ill.

Inclusion Criteria

Not pregnant

I do not have any current illnesses.

I am a woman.

Exclusion Criteria

I have a history of kidney disease.

I have a history of heart disease.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one dose of dexrazoxane at varying dosages to study its effect on Topoisomerase 2b degradation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for degradation of Topoisomerase 2b and 2a in blood samples

48 hours

Blood samples collected

Treatment Details

Interventions

• Dexrazoxane

Trial Overview The study is testing if Dexrazoxane given early can prevent heart damage caused by Doxorubicin, a drug used in cancer treatment. The focus is on preventing heart failure in patients receiving Doxorubicin.

Participant Groups

Group I: Dexrazoxane 500mg/m2 Experimental Treatment 1 Intervention

one dose of 500 mg/m2

Group II: Dexrazoxane 400mg/m2 Experimental Treatment 1 Intervention

one dose of 400mg/m2 dexrazoxane

Group III: Dexrazoxane 300mg/m2 Experimental Treatment 1 Intervention

one dose of 300mg/m2 dexrazoxane

Group IV: Dexrazoxane 200mg/m2 Experimental Treatment 1 Intervention

one dose of 200mg/m2 dexrazoxane

Group V: Dexrazoxane 100mg/m2 Experimental Treatment 1 Intervention

one dose of 100mg/m2 dexrazoxane

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Findings from Research

In a study of 70 breast cancer patients undergoing anthracycline-based chemotherapy, the addition of dexrazoxane did not show a protective effect on ECG parameters associated with arrhythmia, as significant increases were observed in both groups after treatment.

Despite dexrazoxane's known role in preventing heart failure, the study found that ejection fraction decreased in both the dexrazoxane and non-dexrazoxane groups, indicating that it may not effectively protect against arrhythmia-related changes during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dexrazoxane effect on preventing acute cardiac arrhythmia in patients with breast cancer treated with neoadjuvant/adjuvant anthracycline-based chemotherapy. Kaplan, O., Bozdag Kaplan, N.[2022]

Doxorubicin, an anthracycline chemotherapy drug, can cause serious heart damage, leading to cardiomyopathy and heart failure, especially when the total dose exceeds 550 mg/m2.

Dexrazoxane has shown significant potential in preventing doxorubicin-induced heart damage by binding iron and reducing harmful free radicals, with promising results from both animal and human studies, although further research is needed to optimize its use alongside chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity. Seifert, CF., Nesser, ME., Thompson, DF.[2017]

In a study of 205 children with high-risk acute lymphoblastic leukemia (ALL), dexrazoxane did not increase the risk of developing secondary malignant neoplasms (SMNs) compared to those who received doxorubicin alone, with a median follow-up of 6.2 years.

The results support the continued use of dexrazoxane as a cardioprotectant during doxorubicin treatment in pediatric patients, as no SMNs were observed in the dexrazoxane group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. Barry, EV., Vrooman, LM., Dahlberg, SE., et al.[2022]

In a study involving Sprague-Dawley rats, dexrazoxane (DZR) significantly reduced infarct size and improved cardiac function after myocardial infarction, indicating its cardioprotective effects.

DZR treatment was associated with increased capillary density and bone marrow-derived endothelial progenitor cells, suggesting that its mechanism of action may involve promoting neovascularization and reducing apoptosis in heart tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: anti-apoptosis and promoting angiogenesis. Zhou, L., Sung, RY., Li, K., et al.[2013]

In a small study of five patients with preexisting cardiomyopathy, the use of dexrazoxane allowed them to complete anthracycline chemotherapy without significant heart function decline, as their left ventricular ejection fraction (LVEF) only decreased slightly from 39% to 34%.

In contrast, three patients who did not receive dexrazoxane experienced severe heart function deterioration, with LVEF dropping from 42.5% to 18%, leading to symptomatic heart failure and two fatalities, highlighting dexrazoxane's potential as a protective agent in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series. Ganatra, S., Nohria, A., Shah, S., et al.[2022]

Long-term randomized control trials indicate that digoxin may only benefit a minority of heart failure patients, with mixed results from three studies (one positive, two negative).

Angiotensin-converting enzyme inhibitors like captopril and enalapril show consistent and significant improvements in exercise capacity and functional status in heart failure patients, suggesting they should be considered for initial treatment alongside diuretics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of heart failure. A methodological review of the literature. Guyatt, GH.[2018]

In a study of 5436 heart failure patients without diabetes, those treated with candesartan had a lower incidence of developing diabetes (6.0%) compared to those on placebo (7.4%), indicating that candesartan may help prevent diabetes in this population.

Candesartan also reduced the combined risk of death or diabetes, with 25.2% of patients in the candesartan group experiencing this outcome compared to 28.6% in the placebo group, suggesting its potential benefits beyond heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure. Yusuf, S., Ostergren, JB., Gerstein, HC., et al.[2021]

Istaroxime, administered as a 24-hour infusion, significantly improved heart function in patients with acute heart failure, as evidenced by a greater reduction in the E/e' ratio compared to placebo, indicating better diastolic function.

The treatment also increased stroke volume and systolic blood pressure without causing major cardiac adverse effects, such as arrhythmias or hypotension, suggesting it is a safe option for improving heart function in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial. Carubelli, V., Zhang, Y., Metra, M., et al.[2021]

Istaroxime is a promising new treatment for acute heart failure syndromes (AHFS) that works by improving heart contractility and diastolic relaxation without significantly affecting heart rate or blood pressure.

Early human studies show that istaroxime can decrease pulmonary capillary wedge pressure and improve diastolic function, with side effects primarily related to gastrointestinal issues, indicating a need for further research to confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and Na-K-ATPase inhibition: a new promising treatment for acute heart failure syndromes? Khan, H., Metra, M., Blair, JE., et al.[2021]

In a 6-month study involving 305 patients with heart failure, candesartan significantly reduced the progression of heart failure (7.4% in the candesartan group vs. 22.2% in the placebo group), demonstrating a 63.8% risk reduction.

Candesartan also led to a significant decrease in cardiovascular events (10.8% vs. 22.9% in the placebo group), indicating its efficacy in improving heart health in patients who were either untreated or intolerant to ACE inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of angiotensin II receptor antagonist on heart failure]. Matsumori, A.[2021]

References

1. India pubmed.ncbi.nlm.nih.gov

Evaluation of dexrazoxane effect on preventing acute cardiac arrhythmia in patients with breast cancer treated with neoadjuvant/adjuvant anthracycline-based chemotherapy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Dexrazoxane in the prevention of doxorubicin-induced cardiotoxicity. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: anti-apoptosis and promoting angiogenesis. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

The treatment of heart failure. A methodological review of the literature. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and Na-K-ATPase inhibition: a new promising treatment for acute heart failure syndromes? [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

[Effect of angiotensin II receptor antagonist on heart failure]. [2021]