Heart Failure and Reduced Ejection FractionNCT07134972
The Effect of Ozone Treatment on Coronary Flow Reserve in Patients With Heart Failure Having Reduced Ejection Fraction
A study testing Ozone treatment in people with Heart Failure and Reduced Ejection Fraction, run by Ekrem Bilal Karaayvaz at 1 site in Turkey (Türkiye).
Trial summary
The goal of this clinical trial is to determine the effect of ozone treatment in heart failurte with reduced ejection fraction. The main questions it aims to answer are: Does ozone treatment have beneficial effects in heart failure patients? What medical problems do heart failure patients have when taking ozone… Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure and Reduced Ejection Fraction
- What is being tested?
- Ozone treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 14 Jan 2024to 21 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Previosuly known coronary angiography with less than % 50 stenosis
- Echocardiography with ejection fraction of less than % 40
- Patients with previosly planned for ozone treatment for non-chronic disease or conditions
Who cannot join
- Known chronic diseases or conditions that effect endothelial functions.
- Previosly had acute coronary syndrome or stent implantation or any coronary intervention.
- Smokers
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Medicana International Hospital Istanbul
Istanbul
About this study
The goal of this clinical trial is to determine the effect of ozone treatment in heart failurte with reduced ejection fraction. The main questions it aims to answer are:
Does ozone treatment have beneficial effects in heart failure patients? What medical problems do heart failure patients have when taking ozone treatment? Researchers will compare ozone treatment in patients with heart failure to ozone treatment in patients with no heart failure (control group) as well as before and after the ozone treatment in patients with heart failure to see if ozone works to treat heart failure.
Read more
Participants will:
Give blood samples Take 6-minute walk test Be perfomed Echocardiography with CFR (Coronary Flow Reserve) Take drug ABC or a placebo every day for 4 months Visit the clinic twice a week for ozone treatment for 2 months Give blood samples (after the ozone treatment) Take 6-minute walk test (after the ozone treatment) Be perfomed Echocardiography with CFR (Coronary Flow Reserve) (after the ozone treatment)
Read the detailed description
Patients who were previously scheduled for ozone therapy at the ozone therapy clinic of Medicana International Hospital Istanbul for another indication that did not affect the endothelial function of coronary arteries were included in the study. Patients with diseases or conditions that may affect endothelial function such as diabetes mellitus, chronic renal failure, thyroid or liver dysfunction, inflammatory diseases or smoking were excluded. Thirty-eight patients with non-ischemic cardiomyopathy who underwent coronary angiography in the Cardiology Department of Medicana International Hospital Istanbul and had less than 50% stenosis and less than 40% ejection fraction (EF) on transthoracic echocardiography were included in the study. All participants were taking beta-blockers, ACEi and mineralocorticoid receptor antagonists for the treatment of heart failure. A control group of 22 people with similar age, sex and demographic properties and no chronic disease has included to the study.
After the patients were enrolled in the study, blood samples were taken and 6-minute walk test, CFR measurement and transthoracic echocardiography were performed. They were then sent for ozone therapy. Two months later, after ozone therapy, blood samples were taken and 6-minute walk test, CFR measurement and transthoracic echocardiography were performed again.
- Being tested
- Ozone treatment
- Keywords
- ozone treatment, heart failure with reduced ejection fraction, coronary flow reserve
- Medical subject headings
- Heart Failure, Systolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ozone treatmentDrug
Also called Ozone therapy
Ozone treatment was administered to study group only. 90 ml of blood was collected into a vacuum sterile glass bottle (Ozonosan). To prevent clotting, 10 ml of 3.8% Na Citrate solution was added to the glass vial. The blood to citrate volume ratio is 9:1. After blood collection, the O3 concentration is ozonized to 20-50 mcg/ml. After at least 5 minutes of mixing, ozonized blood was infused over 20 minutes. Ozone/oxygen mixture was administered intravenously. Ozone therapy was administered twice a week for a total of 16 sessions.
| Study group | Role | What they receive |
|---|---|---|
| Control Group | No intervention | This group was given no treatment or medication. They had normal echocardiography. They had no heart failure or chronic diseases. |
| Study Group | Experimental | Heart failure patients with reduced ejection fraction was administered ozone treatment and diagnosed before and after the treatment to understand ozone treatment's effect. Receives: Drug: Ozone treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who had acute heart failure.
The ozone treatment is used for heart failure in this study. If any patient had acute heart failure episode, whether it is drug related or not, that patient can no longer participate in the study.
Measured: From start of the treatment to 2 months after the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2025
- Study start14 Jan 2024
- Primary completion21 Dec 2024
- Study completion21 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Heart Failure and Reduced Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Model description
- In our study only the heart failure group have taken ozone treatment. But control groups diagnostic findings were used to compare effect of the treatment.
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ekrem Bilal Karaayvaz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ekrem Bilal Karaayvaz, Istanbul University
- Investigators
- Ekrem Bilal Karaayvaz, Principal investigator, Istanbul University Istanbul Faculty of Medicine, Department of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07134972
- Sponsor's protocol ID
- IstanbulU-EBKaraayvaz-1
- Status last verified
- Sep 2025
- First submitted
- 14 Aug 2025
- Last updated
- 26 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Publications
Sawyer DB. Oxidative stress in heart failure: what are we missing? Am J Med Sci. 2011 Aug;342(2):120-4. doi: 10.1097/MAJ.0b013e3182249fcd.
PubMed 21747279Zuchi C, Tritto I, Carluccio E, Mattei C, Cattadori G, Ambrosio G. Role of endothelial dysfunction in heart failure. Heart Fail Rev. 2020 Jan;25(1):21-30. doi: 10.1007/s10741-019-09881-3.
PubMed 31686283Katz SD. Mechanisms and implications of endothelial dysfunction in congestive heart failure. Curr Opin Cardiol. 1997 May;12(3):259-64. doi: 10.1097/00001573-199705000-00007.
PubMed 9243083Heusch G. Coronary blood flow in heart failure: cause, consequence and bystander. Basic Res Cardiol. 2022 Jan 13;117(1):1. doi: 10.1007/s00395-022-00909-8.
PubMed 35024969Karaayvaz EB, Guz G. Coronary Flow Reserve Changes after Angiotensin Receptor-Neprilysin Inhibitor Treatment in Heart Failure with Reduced Ejection Fraction. Acta Cardiol Sin. 2023 Nov;39(6):871-878. doi: 10.6515/ACS.202311_39(6).20230619C.
PubMed 38022415
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Ozone Treatment on Coronary Flow Reserve in Patients With Heart Failure Having Reduced Ejection Fraction
- ClinicalTrials.gov ID
- NCT07134972
- Acronym / sponsor ID
- IstanbulU-EBKaraayvaz-1
- Keywords
- ozone treatment, heart failure with reduced ejection fraction, coronary flow reserve
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Ekrem Bilal KaraayvazUniversity, hospital or other
- Study start
- 14 Jan 2024 (actual)
- Primary completion
- 21 Dec 2024 (actual)
- Study completion
- 21 Dec 2024 (actual)
- First posted
- 21 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to determine the effect of ozone treatment in heart failurte with reduced ejection fraction. The main questions it aims to answer are:
Does ozone treatment have beneficial effects in heart failure patients? What medical problems do heart failure patients have when taking ozone treatment? Researchers will compare ozone treatment in patients with heart failure to ozone treatment in patients with no heart failure (control group) as well as before and after the ozone treatment in patients with heart failure to see if ozone works to treat heart failure.
Participants will:
Give blood samples Take 6-minute walk test Be perfomed Echocardiography with CFR (Coronary Flow Reserve) Take drug ABC or a placebo every day for 4 months Visit the clinic twice a week for ozone treatment for 2 months Give blood samples (after the ozone treatment) Take 6-minute walk test (after the ozone treatment) Be perfomed Echocardiography with CFR (Coronary Flow Reserve) (after the ozone treatment)
Detailed description
Patients who were previously scheduled for ozone therapy at the ozone therapy clinic of Medicana International Hospital Istanbul for another indication that did not affect the endothelial function of coronary arteries were included in the study. Patients with diseases or conditions that may affect endothelial function such as diabetes mellitus, chronic renal failure, thyroid or liver dysfunction, inflammatory diseases or smoking were excluded. Thirty-eight patients with non-ischemic cardiomyopathy who underwent coronary angiography in the Cardiology Department of Medicana International Hospital Istanbul and had less than 50% stenosis and less than 40% ejection fraction (EF) on transthoracic echocardiography were included in the study. All participants were taking beta-blockers, ACEi and mineralocorticoid receptor antagonists for the treatment of heart failure. A control group of 22 people with similar age, sex and demographic properties and no chronic disease has included to the study.
After the patients were enrolled in the study, blood samples were taken and 6-minute walk test, CFR measurement and transthoracic echocardiography were performed. They were then sent for ozone therapy. Two months later, after ozone therapy, blood samples were taken and 6-minute walk test, CFR measurement and transthoracic echocardiography were performed again.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In our study only the heart failure group have taken ozone treatment. But control groups diagnostic findings were used to compare effect of the treatment.
| Arm | Type | Receives |
|---|---|---|
| Control Group | No intervention | –This group was given no treatment or medication. They had normal echocardiography. They had no heart failure or chronic diseases. |
| Study Group | Experimental | Drug: Ozone treatmentHeart failure patients with reduced ejection fraction was administered ozone treatment and diagnosed before and after the treatment to understand ozone treatment's effect. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Previosuly known coronary angiography with less than % 50 stenosis
- Echocardiography with ejection fraction of less than % 40
- Patients with previosly planned for ozone treatment for non-chronic disease or conditions
Key exclusion criteria (3 listed)
- Known chronic diseases or conditions that effect endothelial functions.
- Previosly had acute coronary syndrome or stent implantation or any coronary intervention.
- Smokers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ozone treatmentAlso: Ozone therapyOzone treatment was administered to study group only. 90 ml of blood was collected into a vacuum sterile glass bottle (Ozonosan). To prevent clotting, 10 ml of 3.8% Na Citrate solution was added to the glass vial. The blood to citrate volume ratio is 9:1. After blood collection, the O3 concentration is ozonized to 20-50 mcg/ml. After at least 5 minutes of mixing, ozonized blood was infused over 20 minutes. Ozone/oxygen mixture was administered intravenously. Ozone therapy was administered twice a week for a total of 16 sessions. | Drug | Study Group |
Primary outcome
Number of patients who had acute heart failure.
Time frame: From start of the treatment to 2 months after the treatment
The ozone treatment is used for heart failure in this study. If any patient had acute heart failure episode, whether it is drug related or not, that patient can no longer participate in the study.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2025.
- Background: PubMed 21747279Sawyer DB. Oxidative stress in heart failure: what are we missing? Am J Med Sci. 2011 Aug;342(2):120-4. doi: 10.1097/MAJ.0b013e3182249fcd.
- Background: PubMed 31686283Zuchi C, Tritto I, Carluccio E, Mattei C, Cattadori G, Ambrosio G. Role of endothelial dysfunction in heart failure. Heart Fail Rev. 2020 Jan;25(1):21-30. doi: 10.1007/s10741-019-09881-3.
- Background: PubMed 9243083Katz SD. Mechanisms and implications of endothelial dysfunction in congestive heart failure. Curr Opin Cardiol. 1997 May;12(3):259-64. doi: 10.1097/00001573-199705000-00007.
- Background: PubMed 35024969Heusch G. Coronary blood flow in heart failure: cause, consequence and bystander. Basic Res Cardiol. 2022 Jan 13;117(1):1. doi: 10.1007/s00395-022-00909-8.
- Results publication: PubMed 38022415Karaayvaz EB, Guz G. Coronary Flow Reserve Changes after Angiotensin Receptor-Neprilysin Inhibitor Treatment in Heart Failure with Reduced Ejection Fraction. Acta Cardiol Sin. 2023 Nov;39(6):871-878. doi: 10.6515/ACS.202311_39(6).20230619C.
- Individual participant dataSharing planned: Yes. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ekrem Bilal Karaayvaz principal investigator
Istanbul University Istanbul Faculty of Medicine, Department of Cardiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ozone treatment in people with Heart Failure and Reduced Ejection Fraction, run by Ekrem Bilal Karaayvaz at 1 site in Turkey (Türkiye).
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 3 inclusion and 3 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: finished, as of the sponsor's last update on 26 Sep 2025. 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 Turkey (Türkiye). 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients who had acute heart failure. (time frame: From start of the treatment to 2 months after the treatment). 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 NCT07134972, which also lists 5 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 26 Sep 2025.