Ozone Therapy in Refractory Ischemic Heart Disease.

NCT03660657 | Terminated Phase 2 DMC

• 3 other identifiers: O3Cardio2018-000201-24PIFUN44/17
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (2)

• 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)

  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).

  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)

  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)

  16 weeks

• Change from Baseline in Montreal Cognitive Assessment (MOCA) questionnaire (at the end of ozone therapy)

  16 weeks

• Change from Baseline in Biochemical cardiac parameters (High sensitive troponin, pro-brain natriuretic peptide (proBNP)) (at the end of ozone therapy)

  16 weeks

• Change from Baseline in Biochemical parameters of oxidative stress (at the end of ozone therapy)

  16 weeks

Study Arms (2)

Ozone Group:

EXPERIMENTAL

Standard treatment + Ozone therapy (O3/O2)

Drug: Ozone

Control Group:

PLACEBO COMPARATOR

Standard treatment + Oxygen (O2)

Drug: Oxygen

Interventions

Ozone DRUG

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.

Also known as: O3

Ozone Group:

Oxygen DRUG

Control Group: Standard treatment + Oxygen (O2) by rectal insufflation. O3/O2 concentration = 0 µg/ml (only O2); 40 sessions in 16 weeks.

Also known as: O2

Control Group:

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%.
• 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.

Sponsors & Collaborators

• Bernardino Clavo, MD, PhD: lead
• Servicio Canario de Salud: collaborator
• Red de Investigación en Servicios de Salud en Enfermedades Crónicas: collaborator
• Fundación Canaria de Investigación Sanitaria: collaborator
• Colegio Oficial de Médicos de Las Palmas: collaborator
• Fundación MAPFRE Guanarteme: collaborator

Study Sites (1)

Dr. Negrin University Hospital

Las Palmas de Gran Canaria, Las Palmas, 35019, Spain

Location

Related Publications (11)

• 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.

  PMID: 28097518 BACKGROUND

• Bocci 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.

  PMID: 19260079 BACKGROUND

• Bocci 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.

  PMID: 21575276 BACKGROUND

• Bocci 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.

  PMID: 25699252 BACKGROUND

• Clavo 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.

  PMID: 12804078 BACKGROUND

• Clavo 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.

  PMID: 15841265 BACKGROUND

• Clavo 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.

  PMID: 28853025 BACKGROUND

• Di 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.

  PMID: 18827966 BACKGROUND

• Giunta 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.

  PMID: 11797116 BACKGROUND

• Martinez-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.

  PMID: 22796450 BACKGROUND

• Bocci 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.

  PMID: 21446774 BACKGROUND

Related Links

• EU Clinical Trials Register (European Union Clinical Trials Register)
• Spanish Clinical Studies Registry

MeSH Terms

Conditions

Myocardial Ischemia; Heart Failure

Interventions

Ozone; Oxygen

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Gases; Inorganic Chemicals; Chalcogens; Elements

Study Officials

• Bernardino Clavo, MD, PhD

  Dr. Negrín University Hospital, Las Palmas, Spain

  STUDY CHAIR

• Pedro G Serrano-Aguilar, MD, PhD

  Servicio de Evaluación. Servicio Canario de Salud. Spain

  STUDY DIRECTOR

• Renata Linertová, PhD

  Servicio de Evaluación. Servicio Canario de Salud. Spain

  PRINCIPAL INVESTIGATOR

• Bernardino Clavo, MD, PhD

  Dr. Negrín University Hospital, Las Palmas, Spain

  PRINCIPAL INVESTIGATOR

• Celestina Amador, MD, PhD

  Dr. Negrín University Hospital, Las Palmas, Spain

  PRINCIPAL INVESTIGATOR

• Francisco Rodríguez-Esparragón, BSc, PhD

  Dr. Negrín University Hospital, Las Palmas, Spain

  PRINCIPAL INVESTIGATOR

• Norberto Santana-Rodríguez, MD, PhD

  King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking of: patients, cardiologist and cardiac surgeons (clinical assessment), investigators obtaining other parameters (quality of life, biochemical and clinical parameters), investigators for statistical analysis
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Head of Research Unit

Model Details: Standard treatment + ozone therapy (O3/O2) versus Standard treatment + oxygen (O2) as placebo

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: September 6, 2018
• Study Start: February 26, 2020
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2020
• Last Updated: April 4, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)