Ischemic Heart DiseasePhase 2/3O3CardioNCT03660657
Ozone Therapy in Refractory Ischemic Heart Disease.
A Phase 2/3 study testing Ozone and Oxygen in people with Ischemic Heart Disease, run by Bernardino Clavo, MD, PhD at 1 site in Spain.
Trial summary
The main objective of this clinical trial is to evaluate the effectiveness and cost-effectiveness of adding ozone therapy to standard management of patients with advanced ischemic heart disease refractory to medical and surgical treatment. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Ischemic Heart Disease
- What is being tested?
- Ozone and Oxygen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteSpain
- Study dates
- 26 Feb 2020to 30 Nov 2020
- Phase
- Phase 2/3
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults with ischemic heart disease, Functional Class III-IV from the NYHA, with symptoms in spite of maximal conventional medical treatment and no suitable to further percutaneous or surgical procedures.
- It should be required clinical diagnosis by the Cardiology Department and confirmation by cardiac catheterization with coronary angiography.
- Ejection Fraction < 40%
- Patients who have signed and dated the study 's specific informed consent.
- Before enrollment, women of childbearing potential should obtain a negative result in the serum or urine pregnancy test at the screening visit, and accept the use of appropriate contraceptive methods at least from the 14 days prior to the first dose of the study drug. up to 14 days after the last one.
Who cannot join
- Age < 18 or > 85 years old.
- Severe valve disease and/or dynamic left ventricular outflow tract obstruction.
- Pregnancy at the time of enrollment.
- Limited walking ability due to neurologic or orthopedic impairments of the legs
- Those who are incapable to fill in the scales used to measure the quality of life variables
- Cerebral vascular accident (CVA or Transient Ischemic Attack (TIA) within the previous 3 months or carotid stenosis > 80%.
Show all 17Show fewer
- Acute myocardial infarction (AMI), Percutaneous coronary intervention (PCI) or transmyocardial laser revascularization (TMR or PMR) within the previous 3 months.
- Hemodynamically or clinically unstable patients.
- Severe or limiting pulmonary diseases.
- Specific liver enzymes [Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) > 5 times the upper limit of normal
- Increased creatinine > 3 times the upper limit of normal or Glomerular Filtration Rate (GFR) < 25 ml/min or who are on chronic renal dialysis.
- Severe peripheral vascular disease with rest pain or significant chronic wounds.
- Uncontrolled cancer disease or severe active systemic infection or HIV.
- Life expectancy < 4 months
- Contraindication or disability for rectal ozone administration or to attend scheduled treatments.
- Known allergy to ozone.
- Patients who do not meet all the inclusion criteria.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Dr. Negrin University Hospital
Las Palmas de Gran Canaria, Las Palmas, 35019
About this study
Official title: Effectiveness and Cost-effectiveness of Ozone Therapy in Patients With Ischemic Heart Disease Refractory to Medical and Surgical Treatment: Randomized, Triple-blind Clinical Trial
The main objective of this clinical trial is to evaluate the effectiveness and cost-effectiveness of adding ozone therapy to standard management of patients with advanced ischemic heart disease refractory to medical and surgical treatment.
Read the detailed description
This study will evaluate the potential role of ozone therapy added to the standard management of patients with symptomatic refractory ischemic heart disease, III-IV functional class of the classification of the New York Heart Association (NYHA).
MAIN OBJECTIVES: 1) to evaluate clinical effect and quality of life related to health (HRQOL) of adding O3 to the standard treatment of these patients. 2) to estimate the additional costs of adding O3 to the standard treatment and to evaluate the cost-effectiveness ratio.
SECONDARY OBJECTIVES: 3) To evaluate the evolution of a) biochemical parameters; b) cardiovascular parameters; c) toxicity of O3. 4) Develop and evaluate the acceptability of a shared decision-making (SDM) tool between professionals and patients.
METHODOLOGY: Phase II-III clinical trial, randomized, triple-blind. Sample size: 18 patients.
TREATMENT: All patients will receive their standard treatment + 40 sessions of rectal insufflation:
- Ozone-Group (n = 9): O3/O2 concentration progressively increased from 10 to 30 µg/ml.
- Control-placebo-Group (n = 9): O3/O2 Concentration = 0 µg/ml (only O2).
Main Variables: 1) changes in the self-perceived quality of life (Minnesota scale). 2) Direct costs.
Secondary Variables: 1) biochemical parameters; 2) Cardiovascular parameters; 3) Side effects. 4) acceptability of patients to a shared decision-making (SDM) tool.
Length of treatment: 16 weeks.
Follow-up: 16 weeks after completion of O3.
Assessments: 1) Pre-O3 (basal), 2) pos-O3 (end of O3), 3) 4 months pos-O3.
Planned length of clinical trial: 36 months.
- Conditions
- Ischemic Heart Disease
- Being tested
- Ozone, Oxygen
- Keywords
- complementary and integrative medicine, cost-effectiveness ratio, ischemic heart disease, heart failure, ozone therapy, quality of life related to health, shared decision-making tool
- Medical subject headings
- Myocardial Ischemia, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OzoneDrug
Also called O3
Ozone Group: Standard treatment + Ozone therapy (O3/O2) by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 µg/ml; 40 sessions in 16 weeks.
OxygenDrug
Also called O2
Control Group: Standard treatment + Oxygen (O2) by rectal insufflation. O3/O2 concentration = 0 µg/ml (only O2); 40 sessions in 16 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Ozone Group: | Experimental | Standard treatment + Ozone therapy (O3/O2) Receives: Drug: Ozone |
| Control Group: | Placebo comparator | Standard treatment + Oxygen (O2) Receives: Drug: Oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quality of Life (QoL) measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (at the end of ozone therapy)
Self-reported evaluation of 21 physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each item is scored from 0 (no affected) to 5 (very much affected). Total range from 0 (best) to 105 (worst)
Measured: 16 weeks
Direct Hospital Cost (at the end of ozone therapy)
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros).
Measured: 16 weeks
Secondary outcomes (30)
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at the end of ozone therapy)
Self-reported evaluation of: a) 5 physical and emotional items scored in five levels, from 1 (best: I have no problem) to 5 (worst: I have extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine)
Measured: 16 weeks
Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36) questionnaire (at the end of ozone therapy)
Self-reported evaluation of 36 items (0 = worst, 100 = best). Final accumulated total range from 0 (worst) to 100 (best)
Measured: 16 weeks
Change from Baseline in Montreal Cognitive Assessment (MOCA) questionnaire (at the end of ozone therapy)
Assessment of 8 types of cognitive abilities by a total 30-point test (0 = worst, 30 = best)
Measured: 16 weeks
Change from Baseline in Biochemical cardiac parameters (High sensitive troponin, pro-brain natriuretic peptide (proBNP)) (at the end of ozone therapy)
Serum levels of high sensitive troponin and proBNP
Measured: 16 weeks
Change from Baseline in Biochemical parameters of oxidative stress (at the end of ozone therapy)
Serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals
Measured: 16 weeks
Change from Baseline in Biochemical parameters of inflammation (at the end of ozone therapy)
Serum levels of pro-inflammatory interleukins and TNFalpha
Measured: 16 weeks
Change from Baseline (by Echocardiograpy) of: left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) (at the end of ozone therapy)
Measurement of volume (in ml) of LVEDV and LVESV.
Measured: 16 weeks
Change from Baseline (by Echocardiograpy) of left ventricular ejection fraction (LVEF) (at the end of ozone therapy)
Measurement (in percentage) of LVEF
Measured: 16 weeks
Change from Baseline in Six-minute walk test (6MWT) (at the end of ozone therapy)
Assessment of functional exercise capacity according to the walking distance covered over a time of 6 minutes (in meters)
Measured: 16 weeks
Change from Baseline in cerebral blood flow by Transcranial doppler (at the end of ozone therapy)
Doppler ultrasound evaluation of systolic and diastolic velocity in middle cerebral arteries (in cm/s)
Measured: 16 weeks
Change from Baseline in Hyperspectral image of the supraciliary area (at the end of ozone therapy)
Assessment of the percentage of reflectance for each wavelength
Measured: 16 weeks
Change from Baseline in lower limb blood flow by Doppler ultrasound (at the end of ozone therapy)
Doppler ultrasound evaluation of systolic and diastolic velocity in lower limbs (in cm/s)
Measured: 16 weeks
Change from Baseline in Hyperspectral image of lower limbs (at the end of ozone therapy)
Assessment of the percentage of reflectance for each wavelength
Measured: 16 weeks
Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at the end of ozone therapy)
Number of events that are fatal, life threatening, leading to or prolonging a stay in hospital, or resulting in severe disability
Measured: 16 weeks
Quality of Life (QoL) measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (at 32 weeks)
Self-reported evaluation of 21 physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each item is scored from 0 (no affected) to 5 (very much affected). Total range from 0 (best) to 105 (worst)
Measured: 32 weeks
Direct Hospital Cost (at 32 weeks)
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros)
Measured: 32 weeks
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at 32 weeks)
Self-reported evaluation of: a) 5 physical and emotional items scored in five levels, from 1 (best: I have no problem) to 5 (worst: I have extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine)
Measured: 32 weeks
Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36) questionnaire (at 32 weeks)
Self-reported evaluation of 36 items (0 = worst, 100 = best). Final accumulated total range from 0 (worst) to 100 (best)
Measured: 32 weeks
Change from Baseline in Montreal Cognitive Assessment (MOCA) questionnaire (at 32 weeks)
Assessment of 8 types of cognitive abilities by a total 30-point test (0 = worst, 30 = best)
Measured: 32 weeks
Change from Baseline in Biochemical cardiac parameters (High sensitive troponin, pro-brain natriuretic peptide (proBNP)) (at 32 weeks)
Serum levels of high sensitive troponin and proBNP
Measured: 32 weeks
Change from Baseline in Biochemical parameters of oxidative stress (at 32 weeks)
Serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals
Measured: 32 weeks
Change from Baseline in Biochemical parameters of inflammation (at 32 weeks)
Serum levels of pro-inflammatory interleukins and TNFalpha
Measured: 32 weeks
Change from Baseline (by Echocardiograpy) of: left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) (at 32 weeks)
Measurement of volume (in ml) of LVEDV and LVESV.
Measured: 32 weeks
Change from Baseline (by Echocardiograpy) of left ventricular ejection fraction (LVEF) (at 32 weeks)
Measurement (in percentage) of LVEF
Measured: 32 weeks
Change from Baseline in Six-minute walk test (6MWT) (at 32 weeks)
Assessment of functional exercise capacity according to the walking distance covered over a time of 6 minutes (in meters)
Measured: 32 weeks
Change from Baseline in cerebral blood flow by Transcranial doppler (at 32 weeks)
Doppler ultrasound evaluation of systolic and diastolic velocity in middle cerebral arteries (in cm/s)
Measured: 32 weeks
Change from Baseline in Hyperspectral image of the supraciliary area (at 32 weeks)
Assessment of the percentage of reflectance for each wavelength
Measured: 32 weeks
Change from Baseline in lower limb blood flow by Doppler ultrasound (at 32 weeks)
Doppler ultrasound evaluation of systolic and diastolic velocity in lower limbs (in cm/s)
Measured: 32 weeks
Change from Baseline in Hyperspectral image of lower limbs (at 32 weeks)
Assessment of the percentage of reflectance for each wavelength
Measured: 32 weeks
Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at 32 weeks)
Number of events that are fatal, life threatening, leading to or prolonging a stay in hospital, or resulting in severe disability
Measured: 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2018
- Study start26 Feb 2020
- Primary completion30 Nov 2020
- Study completion30 Nov 2020
Why it stopped: Very low recruitment. During COVID-19 pandemic these are patients of high risk.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Ischemic Heart DiseaseStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Standard treatment + ozone therapy (O3/O2) versus Standard treatment + oxygen (O2) as placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bernardino Clavo, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Servicio Canario de Salud, Red de Investigación en Servicios de Salud en Enfermedades Crónicas, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Colegio Oficial de Médicos de Las Palmas, Fundación MAPFRE Guanarteme
- Responsible party
- Sponsor-investigator, Bernardino Clavo, MD, PhD, Hospital Universitario de Gran Canaria Doctor Negrín
- Investigators
- Bernardino Clavo, MD, PhD, Study chair, Dr. Negrín University Hospital, Las Palmas, SpainPedro G Serrano-Aguilar, MD, PhD, Study director, Servicio de Evaluación. Servicio Canario de Salud. SpainRenata Linertová, PhD, Principal investigator, Servicio de Evaluación. Servicio Canario de Salud. SpainBernardino Clavo, MD, PhD, Principal investigator, Dr. Negrín University Hospital, Las Palmas, SpainCelestina Amador, MD, PhD, Principal investigator, Dr. Negrín University Hospital, Las Palmas, SpainFrancisco Rodríguez-Esparragón, BSc, PhD, Principal investigator, Dr. Negrín University Hospital, Las Palmas, SpainNorberto Santana-Rodríguez, MD, PhD, Principal investigator, King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03660657
- Sponsor's protocol ID
- O3Cardio
- Other IDs
- 2018-000201-24, 2018-000201-24, PIFUN44/17, 2018
- Acronym
- O3Cardio
- Status last verified
- Apr 2022
- First submitted
- 23 Aug 2018
- Last updated
- 4 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Buyuklu M, Kandemir FM, Set T, Bakirci EM, Degirmenci H, Hamur H, Topal E, Kucukler S, Turkmen K. Beneficial Effects of Ozone Therapy on Oxidative Stress, Cardiac Functions and Clinical Findings in Patients with Heart Failure Reduced Ejection Fraction. Cardiovasc Toxicol. 2017 Oct;17(4):426-433. doi: 10.1007/s12012-017-9400-8.
PubMed 28097518Bocci V, Borrelli E, Travagli V, Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev. 2009 Jul;29(4):646-82. doi: 10.1002/med.20150.
PubMed 19260079Bocci VA, Zanardi I, Travagli V. Ozone acting on human blood yields a hormetic dose-response relationship. J Transl Med. 2011 May 17;9:66. doi: 10.1186/1479-5876-9-66.
PubMed 21575276Bocci V, Valacchi G. Nrf2 activation as target to implement therapeutic treatments. Front Chem. 2015 Feb 2;3:4. doi: 10.3389/fchem.2015.00004. eCollection 2015.
PubMed 25699252Clavo B, Perez JL, Lopez L, Suarez G, Lloret M, Rodriguez V, Macias D, Santana M, Morera J, Fiuza D, Robaina F, Gunderoth M. Effect of ozone therapy on muscle oxygenation. J Altern Complement Med. 2003 Apr;9(2):251-6. doi: 10.1089/10755530360623365.
PubMed 12804078Clavo B, Catala L, Perez JL, Rodriguez V, Robaina F. Ozone Therapy on Cerebral Blood Flow: A Preliminary Report. Evid Based Complement Alternat Med. 2004 Dec;1(3):315-319. doi: 10.1093/ecam/neh039. Epub 2004 Oct 6.
PubMed 15841265Clavo B, Eltobgy K, Caballero E, Abad C, Rodriguez-Esparragon F, Santana-Rodriguez N. Is There a Place for Ozone Therapy in Patients with Heart Failure? Cardiovasc Toxicol. 2017 Oct;17(4):496-497. doi: 10.1007/s12012-017-9423-1. No abstract available.
PubMed 28853025Di Filippo C, Marfella R, Capodanno P, Ferraraccio F, Coppola L, Luongo M, Mascolo L, Luongo C, Capuano A, Rossi F, D'Amico M. Acute oxygen-ozone administration to rats protects the heart from ischemia reperfusion infarct. Inflamm Res. 2008 Oct;57(10):445-9. doi: 10.1007/s00011-008-7237-0.
PubMed 18827966Giunta R, Coppola A, Luongo C, Sammartino A, Guastafierro S, Grassia A, Giunta L, Mascolo L, Tirelli A, Coppola L. Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease. Ann Hematol. 2001 Dec;80(12):745-8. doi: 10.1007/s002770100377. Epub 2001 Oct 13.
PubMed 11797116Martinez-Sanchez G, Delgado-Roche L, Diaz-Batista A, Perez-Davison G, Re L. Effects of ozone therapy on haemostatic and oxidative stress index in coronary artery disease. Eur J Pharmacol. 2012 Sep 15;691(1-3):156-62. doi: 10.1016/j.ejphar.2012.07.010. Epub 2012 Jul 13.
PubMed 22796450Bocci V, Zanardi I, Travagli V. Ozone: a new therapeutic agent in vascular diseases. Am J Cardiovasc Drugs. 2011;11(2):73-82. doi: 10.2165/11539890-000000000-00000.
PubMed 21446774
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness and Cost-effectiveness of Ozone Therapy in Patients With Ischemic Heart Disease Refractory to Medical and Surgical Treatment: Randomized, Triple-blind Clinical Trial
- ClinicalTrials.gov ID
- NCT03660657
- Acronym / sponsor ID
- O3Cardio / O3Cardio
- Conditions
- Ischemic Heart Disease
- Keywords
- complementary and integrative medicine, cost-effectiveness ratio, ischemic heart disease, heart failure, ozone therapy, quality of life related to health, shared decision-making tool
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Very low recruitment. During COVID-19 pandemic these are patients of high risk.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Bernardino Clavo, MD, PhDUniversity, hospital or other
- Collaborators
- Servicio Canario de Salud, Red de Investigación en Servicios de Salud en Enfermedades Crónicas, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Colegio Oficial de Médicos de Las Palmas, Fundación MAPFRE Guanarteme
- Study start
- 26 Feb 2020 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 30 Nov 2020 (actual)
- First posted
- 6 Sep 2018 (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 main objective of this clinical trial is to evaluate the effectiveness and cost-effectiveness of adding ozone therapy to standard management of patients with advanced ischemic heart disease refractory to medical and surgical treatment.
Detailed description
This study will evaluate the potential role of ozone therapy added to the standard management of patients with symptomatic refractory ischemic heart disease, III-IV functional class of the classification of the New York Heart Association (NYHA).
MAIN OBJECTIVES: 1) to evaluate clinical effect and quality of life related to health (HRQOL) of adding O3 to the standard treatment of these patients. 2) to estimate the additional costs of adding O3 to the standard treatment and to evaluate the cost-effectiveness ratio.
SECONDARY OBJECTIVES: 3) To evaluate the evolution of a) biochemical parameters; b) cardiovascular parameters; c) toxicity of O3. 4) Develop and evaluate the acceptability of a shared decision-making (SDM) tool between professionals and patients.
METHODOLOGY: Phase II-III clinical trial, randomized, triple-blind. Sample size: 18 patients.
TREATMENT: All patients will receive their standard treatment + 40 sessions of rectal insufflation:
- Ozone-Group (n = 9): O3/O2 concentration progressively increased from 10 to 30 µg/ml.
- Control-placebo-Group (n = 9): O3/O2 Concentration = 0 µg/ml (only O2).
Main Variables: 1) changes in the self-perceived quality of life (Minnesota scale). 2) Direct costs.
Secondary Variables: 1) biochemical parameters; 2) Cardiovascular parameters; 3) Side effects. 4) acceptability of patients to a shared decision-making (SDM) tool.
Length of treatment: 16 weeks.
Follow-up: 16 weeks after completion of O3.
Assessments: 1) Pre-O3 (basal), 2) pos-O3 (end of O3), 3) 4 months pos-O3.
Planned length of clinical trial: 36 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Standard treatment + ozone therapy (O3/O2) versus Standard treatment + oxygen (O2) as placebo
| Arm | Type | Receives |
|---|---|---|
| Ozone Group: | Experimental | Drug: OzoneStandard treatment + Ozone therapy (O3/O2) |
| Control Group: | Placebo comparator | Drug: OxygenStandard treatment + Oxygen (O2) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults with ischemic heart disease, Functional Class III-IV from the NYHA, with symptoms in spite of maximal conventional medical treatment and no suitable to further percutaneous or surgical procedures.
- It should be required clinical diagnosis by the Cardiology Department and confirmation by cardiac catheterization with coronary angiography.
- Ejection Fraction < 40%
- Patients who have signed and dated the study 's specific informed consent.
- Before enrollment, women of childbearing potential should obtain a negative result in the serum or urine pregnancy test at the screening visit, and accept the use of appropriate contraceptive methods at least from the 14 days prior to the first dose of the study drug. up to 14 days after the last one.
Key exclusion criteria (17 listed)
- Age < 18 or > 85 years old.
- Severe valve disease and/or dynamic left ventricular outflow tract obstruction.
- Pregnancy at the time of enrollment.
- Limited walking ability due to neurologic or orthopedic impairments of the legs
- Those who are incapable to fill in the scales used to measure the quality of life variables
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 |
|---|---|---|
| OzoneAlso: O3Ozone Group: Standard treatment + Ozone therapy (O3/O2) by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 µg/ml; 40 sessions in 16 weeks. | Drug | Ozone Group: |
| OxygenAlso: O2Control Group: Standard treatment + Oxygen (O2) by rectal insufflation. O3/O2 concentration = 0 µg/ml (only O2); 40 sessions in 16 weeks. | Drug | Control Group: |
Primary outcome
Quality of Life (QoL) measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (at the end of ozone therapy)
Time frame: 16 weeks
Self-reported evaluation of 21 physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each item is scored from 0 (no affected) to 5 (very much affected). Total range from 0 (best) to 105 (worst)
Direct Hospital Cost (at the end of ozone therapy)
Time frame: 16 weeks
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros).
30 secondary outcomes
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36) questionnaire (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in Montreal Cognitive Assessment (MOCA) questionnaire (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in Biochemical cardiac parameters (High sensitive troponin, pro-brain natriuretic peptide (proBNP)) (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in Biochemical parameters of oxidative stress (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in Biochemical parameters of inflammation (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline (by Echocardiograpy) of: left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline (by Echocardiograpy) of left ventricular ejection fraction (LVEF) (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in Six-minute walk test (6MWT) (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in cerebral blood flow by Transcranial doppler (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in Hyperspectral image of the supraciliary area (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in lower limb blood flow by Doppler ultrasound (at the end of ozone therapy)
Time frame: 16 weeks
Change from Baseline in Hyperspectral image of lower limbs (at the end of ozone therapy)
Time frame: 16 weeks
Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at the end of ozone therapy)
Time frame: 16 weeks
Quality of Life (QoL) measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (at 32 weeks)
Time frame: 32 weeks
Direct Hospital Cost (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36) questionnaire (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in Montreal Cognitive Assessment (MOCA) questionnaire (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in Biochemical cardiac parameters (High sensitive troponin, pro-brain natriuretic peptide (proBNP)) (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in Biochemical parameters of oxidative stress (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in Biochemical parameters of inflammation (at 32 weeks)
Time frame: 32 weeks
Change from Baseline (by Echocardiograpy) of: left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) (at 32 weeks)
Time frame: 32 weeks
Change from Baseline (by Echocardiograpy) of left ventricular ejection fraction (LVEF) (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in Six-minute walk test (6MWT) (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in cerebral blood flow by Transcranial doppler (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in Hyperspectral image of the supraciliary area (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in lower limb blood flow by Doppler ultrasound (at 32 weeks)
Time frame: 32 weeks
Change from Baseline in Hyperspectral image of lower limbs (at 32 weeks)
Time frame: 32 weeks
Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at 32 weeks)
Time frame: 32 weeks
Results and safety
The study was stopped early (reason given: Very low recruitment. During COVID-19 pandemic these are patients of high risk.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2022.
- Background: PubMed 28097518Buyuklu M, Kandemir FM, Set T, Bakirci EM, Degirmenci H, Hamur H, Topal E, Kucukler S, Turkmen K. Beneficial Effects of Ozone Therapy on Oxidative Stress, Cardiac Functions and Clinical Findings in Patients with Heart Failure Reduced Ejection Fraction. Cardiovasc Toxicol. 2017 Oct;17(4):426-433. doi: 10.1007/s12012-017-9400-8.
- Background: PubMed 19260079Bocci V, Borrelli E, Travagli V, Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev. 2009 Jul;29(4):646-82. doi: 10.1002/med.20150.
- Background: PubMed 21575276Bocci VA, Zanardi I, Travagli V. Ozone acting on human blood yields a hormetic dose-response relationship. J Transl Med. 2011 May 17;9:66. doi: 10.1186/1479-5876-9-66.
- Background: PubMed 25699252Bocci V, Valacchi G. Nrf2 activation as target to implement therapeutic treatments. Front Chem. 2015 Feb 2;3:4. doi: 10.3389/fchem.2015.00004. eCollection 2015.
- Background: PubMed 12804078Clavo B, Perez JL, Lopez L, Suarez G, Lloret M, Rodriguez V, Macias D, Santana M, Morera J, Fiuza D, Robaina F, Gunderoth M. Effect of ozone therapy on muscle oxygenation. J Altern Complement Med. 2003 Apr;9(2):251-6. doi: 10.1089/10755530360623365.
- Background: PubMed 15841265Clavo B, Catala L, Perez JL, Rodriguez V, Robaina F. Ozone Therapy on Cerebral Blood Flow: A Preliminary Report. Evid Based Complement Alternat Med. 2004 Dec;1(3):315-319. doi: 10.1093/ecam/neh039. Epub 2004 Oct 6.
- Background: PubMed 28853025Clavo B, Eltobgy K, Caballero E, Abad C, Rodriguez-Esparragon F, Santana-Rodriguez N. Is There a Place for Ozone Therapy in Patients with Heart Failure? Cardiovasc Toxicol. 2017 Oct;17(4):496-497. doi: 10.1007/s12012-017-9423-1. No abstract available.
- Background: PubMed 18827966Di Filippo C, Marfella R, Capodanno P, Ferraraccio F, Coppola L, Luongo M, Mascolo L, Luongo C, Capuano A, Rossi F, D'Amico M. Acute oxygen-ozone administration to rats protects the heart from ischemia reperfusion infarct. Inflamm Res. 2008 Oct;57(10):445-9. doi: 10.1007/s00011-008-7237-0.
- Background: PubMed 11797116Giunta R, Coppola A, Luongo C, Sammartino A, Guastafierro S, Grassia A, Giunta L, Mascolo L, Tirelli A, Coppola L. Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease. Ann Hematol. 2001 Dec;80(12):745-8. doi: 10.1007/s002770100377. Epub 2001 Oct 13.
- Background: PubMed 22796450Martinez-Sanchez G, Delgado-Roche L, Diaz-Batista A, Perez-Davison G, Re L. Effects of ozone therapy on haemostatic and oxidative stress index in coronary artery disease. Eur J Pharmacol. 2012 Sep 15;691(1-3):156-62. doi: 10.1016/j.ejphar.2012.07.010. Epub 2012 Jul 13.
- Background: PubMed 21446774Bocci V, Zanardi I, Travagli V. Ozone: a new therapeutic agent in vascular diseases. Am J Cardiovasc Drugs. 2011;11(2):73-82. doi: 10.2165/11539890-000000000-00000.
- EU Clinical Trials Register (European Union Clinical Trials Register)Link provided by the sponsor.
- Spanish Clinical Studies RegistryLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Bernardino Clavo, MD, PhD study chair
Dr. Negrín University Hospital, Las Palmas, Spain
Pedro G Serrano-Aguilar, MD, PhD study director
Servicio de Evaluación. Servicio Canario de Salud. Spain
Renata Linertová, PhD principal investigator
Servicio de Evaluación. Servicio Canario de Salud. Spain
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ozone and Oxygen in people with Ischemic Heart Disease, run by Bernardino Clavo, MD, PhD at 1 site in Spain.
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 5 inclusion and 17 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: stopped early, as of the sponsor's last update on 4 Apr 2022. 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 Spain. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Very low recruitment. During COVID-19 pandemic these are patients of high risk.). Results are not available in the source record.
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?
Quality of Life (QoL) measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (at the end of ozone therapy) (time frame: 16 weeks). 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 NCT03660657, which also lists 11 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 4 Apr 2022.