Oxygen Therapy in Patients With Chronic Heart Failure With Reduced Ejection Fraction

Chronic Heart Failure Clinical Trial

— ROXIC  

Official title:

Impact of Oxygen Therapy on Readmissions of Patients With Chronic Heart Failure With Reduced Ejection Fraction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05913739
• Other study ID #: ROXIC
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta
• Contact: Marc Bonnin Vilaplana, MD
• Phone: +34 972 94 02 00
• Email: mbonnin.girona.ics[@]gencat.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess patients with chronic heart failure and moderate-severe ventricular dysfunction (left ventricular ejection fraction (FEVE) <40%) with nocturnal desaturation (mean Oxygen saturation (SatO2) <90% and/or Cummulative time (TC) <90% > 22 minutes) without underlying respiratory disease, oxygen treatment during hours of night rest will reduce exacerbations, improve the ability to effort, sleep quality and poor prognostic parameters of heart failure, compared to patients not receiving oxygen treatment.

Description:

36 patients will attend at baseline, monthly, 3-month and 6-monthly visits.

BASELINE VISIT After being informed about the study and potential risks, all patients giving written informed consent, will be randomized (according to the list) receiving oxygen therapy (treatment group) and those not receiving this treatment (control group).

The following information will be collected:

• Demographics, pathological history, concomitant medication.

• Physical examination, vital signs (pressure, heart rate, weight)

• Doppler echocardiography (an echocardiography performed in the last 6 months will be accepted)

• Analytical determination of biomarkers NT-proBNP and ultrasensitive troponin.

• Assessment of baseline functional class by NYHA classification.

• Respiratory function tests: spirometry and diffusion (will accept tests performed in the last 6 months).

• Arterial blood gases.

• Nocturnal respiratory polygraphy.

• Exercise capacity with the 6-minute walk test (P6MM)

• Evaluation of health-related quality of life with the Minnesota questionnaire

• Assessment of sleep quality using the Pittsburgh questionnaire

If the patient belongs to the treatment group, the intervention will begin with oxygen therapy with a static concentrator and nasal cannula during the night at home, with a minimum compliance of six hours, following the usual clinical practice. Overnight pulse oximetry at home with oxygen will be performed to confirm if the prescribed flow rate is adequate to achieve a mean SatO2 >90% and/or that the correction of the CT90. If this is not achieved, it will be repeated, modifying the oxygen flow until the target is reached.

The control group will not undergo this intervention.

The rest of the medical treatment will be carried out according to the usual protocol of the Heart Failure Unit.

Follow up visits:

Clinical follow-up will be done at one month, three months and six months after the start of the intervention in the Chronic Respiratory Pathology Unit of Pneumology.

At 1 and 3 months

• Analytical determination of biomarkers nt-proBNP and ultrasensitive troponin (TnThs).

• Baseline functional class will be collected by New York Heart Association (NYHA) classification.

• Physical examination, vital signs (blood pressure (BP), Heart rate (HR), weight).

• Adverse effects and concomitant medication.

At 6 months

• Analytical determination of biomarkers nt-proBNP and ultrasensitive troponin (TnThs).

• Baseline functional class by NYHA classification will be collected.

• Physical examination, vital signs (BP, HR, weight).

• Evaluation of exercise capacity will be done by means of the 6-minute walk test (PM6M).

• Nocturnal pulse oximetry of control: treatment group with oxygen to evaluate the response and control group without oxygen to evaluate the evolution.

• Assessment of health-related quality of life with the Minnesota questionnaire.

• Sleep quality will be assessed using the Pittsburgh questionnaire.

• Adverse effects and concomitant medication.

In the follow-up periods (1, 3 and 6 months), the number of decompensations will be recorded:

• Hospitalizations for heart failure.

• Emergency care for heart failure requiring at least one dose of intravenous diuretic treatment.

• Need for outpatient intravenous depletive treatment due to the presence of congestive signs.

The study will be considered completed after 6 months of follow-up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: December 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients > 18 years old.

• Diagnosis and clinic of chronic heart failure with ventricular dysfunction with left ventricular ejection fraction (LVEF) <40% under optimal medical treatment regardless of its etiology and having presented at least one episode of decompensation (visits to the emergency room, hospitalizations and/or need for intravenous depletive treatment) during the last year.

• Nocturnal desaturation defined as mean SatO2 <90% and/or Cummulative time (TC) <90>22 minutes to nocturnal pulse oximetry done at home.

• Signed informed consent

Exclusion Criteria:

• Chronic lung disease (includes chronic obstructive pulmonary disease with Pulmonary respiratory function (PRF) (forced expiratory volume at one second/forced vital capacity (FEV1/FVC) <70%), diffuse interstitial diseases, pulmonary hypertension of respiratory).

• Obstructive sleep apnea-hypopnea syndrome (OSAHS) with Apnea hypopnea index (AHI) > 14.9.

• Previous treatment with oxygen therapy.

• Not agreeing to attend periodic cardiology visits.

• Being part of other clinical studies that contraindicate an intervention.

• Pregnant or breastfeeding women.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure
• Hypoxia
• Oxygen Deficiency

Intervention

Other:
• Oxygen Therapy
Nocturnal oxygen therapy minimum 6 hours

Locations

Country	Name	City	State
Spain	University Hospital of Girona Dr. Josep Trueta	Girona

Sponsors (1)

Lead Sponsor	Collaborator
Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta

Country where clinical trial is conducted

Spain, 

References & Publications (18)

Bekfani T, Abraham WT. Current and future developments in the field of central sleep apnoea. Europace. 2016 Aug;18(8):1123-34. doi: 10.1093/europace/euv435. Epub 2016 May 26. — View Citation

Bradley TD, Logan AG, Kimoff RJ, Series F, Morrison D, Ferguson K, Belenkie I, Pfeifer M, Fleetham J, Hanly P, Smilovitch M, Tomlinson G, Floras JS; CANPAP Investigators. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med. 2005 Nov 10;353(19):2025-33. doi: 10.1056/NEJMoa051001. — View Citation

Cowie MR, Woehrle H, Wegscheider K, Angermann C, d'Ortho MP, Erdmann E, Levy P, Simonds AK, Somers VK, Zannad F, Teschler H. Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure. N Engl J Med. 2015 Sep 17;373(12):1095-105. doi: 10.1056/NEJMoa1506459. Epub 2015 Sep 1. — View Citation

Damy T, Margarit L, Noroc A, Bodez D, Guendouz S, Boyer L, Drouot X, Lamine A, Paulino A, Rappeneau S, Stoica MH, Dubois-Rande JL, Adnot S, Hittinger L, d'Ortho MP. Prognostic impact of sleep-disordered breathing and its treatment with nocturnal ventilation for chronic heart failure. Eur J Heart Fail. 2012 Sep;14(9):1009-19. doi: 10.1093/eurjhf/hfs085. Epub 2012 Jun 22. — View Citation

du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, King TE Jr, Lancaster L, Noble PW, Sahn SA, Thomeer M, Valeyre D, Wells AU. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. 2011 Dec 15;184(12):1382-9. doi: 10.1164/rccm.201105-0840OC. Epub 2011 Sep 22. — View Citation

Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA; PAFS consensus group. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. Pilot Feasibility Stud. 2016 Oct 21;2:64. doi: 10.1186/s40814-016-0105-8. eCollection 2016. — View Citation

Gottlieb JD, Schwartz AR, Marshall J, Ouyang P, Kern L, Shetty V, Trois M, Punjabi NM, Brown C, Najjar SS, Gottlieb SS. Hypoxia, not the frequency of sleep apnea, induces acute hemodynamic stress in patients with chronic heart failure. J Am Coll Cardiol. 2009 Oct 27;54(18):1706-12. doi: 10.1016/j.jacc.2009.08.016. — View Citation

Julious, S.A. Sample size of 12 per group rule of thumb for a pilot study. .Pharmaceutical Statistics. 2005; 4: 287-291.

Khayat R, Jarjoura D, Porter K, Sow A, Wannemacher J, Dohar R, Pleister A, Abraham WT. Sleep disordered breathing and post-discharge mortality in patients with acute heart failure. Eur Heart J. 2015 Jun 14;36(23):1463-9. doi: 10.1093/eurheartj/ehu522. Epub 2015 Jan 29. — View Citation

Levi-Valensi P, Weitzenblum E, Rida Z, Aubry P, Braghiroli A, Donner C, Aprill M, Zielinski J, Wurtemberger G. Sleep-related oxygen desaturation and daytime pulmonary haemodynamics in COPD patients. Eur Respir J. 1992 Mar;5(3):301-7. Erratum In: Eur Respir J 1992 May;5(5):645. — View Citation

Oldenburg O, Wellmann B, Buchholz A, Bitter T, Fox H, Thiem U, Horstkotte D, Wegscheider K. Nocturnal hypoxaemia is associated with increased mortality in stable heart failure patients. Eur Heart J. 2016 Jun 1;37(21):1695-703. doi: 10.1093/eurheartj/ehv624. Epub 2015 Nov 26. — View Citation

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-2200. doi: 10.1093/eurheartj/ehw128. Epub 2016 May 20. No abstract available. Erratum In: Eur Heart J. 2016 Dec 30;: — View Citation

Shigemitsu M, Nishio K, Kusuyama T, Itoh S, Konno N, Katagiri T. Nocturnal oxygen therapy prevents progress of congestive heart failure with central sleep apnea. Int J Cardiol. 2007 Feb 14;115(3):354-60. doi: 10.1016/j.ijcard.2006.03.018. Epub 2006 Jun 23. — View Citation

Sim J, Lewis M. The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency. J Clin Epidemiol. 2012 Mar;65(3):301-8. doi: 10.1016/j.jclinepi.2011.07.011. Epub 2011 Dec 9. — View Citation

Toyama T, Seki R, Kasama S, Isobe N, Sakurai S, Adachi H, Hoshizaki H, Oshima S, Taniguchi K. Effectiveness of nocturnal home oxygen therapy to improve exercise capacity, cardiac function and cardiac sympathetic nerve activity in patients with chronic heart failure and central sleep apnea. Circ J. 2009 Feb;73(2):299-304. doi: 10.1253/circj.cj-07-0297. Epub 2008 Dec 27. — View Citation

Watanabe E, Kiyono K, Matsui S, Somers VK, Sano K, Hayano J, Ichikawa T, Kawai M, Harada M, Ozaki Y. Prognostic Importance of Novel Oxygen Desaturation Metrics in Patients With Heart Failure and Central Sleep Apnea. J Card Fail. 2017 Feb;23(2):131-137. doi: 10.1016/j.cardfail.2016.09.004. Epub 2016 Sep 9. — View Citation

Yi H, Shin K, Shin C. Development of the sleep quality scale. J Sleep Res. 2006 Sep;15(3):309-16. doi: 10.1111/j.1365-2869.2006.00544.x. Erratum In: J Sleep Res. 2006 Dec;15(4):465. — View Citation

Yumino D, Bradley TD. Central sleep apnea and Cheyne-Stokes respiration. Proc Am Thorac Soc. 2008 Feb 15;5(2):226-36. doi: 10.1513/pats.200708-129MG. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nocturnal oxygen therapy at home in patients with heart failure heart rate and nocturnal desaturation can reduce the number of heart failure decompensations cardiac arrest.	To assess whether treatment with nocturnal oxygen therapy at home in patients with heart failure heart rate and nocturnal desaturation (mean SatO2 <90% and/or CT <90%>22 minutes) no AOS manages to reduce the number of heart failure decompensations cardiac arrest (hospitalizations, visits to the emergency room or the need for depletive treatment intravenously) compared with patients not receiving oxygen therapy.	changes from baseline to 6th month
Secondary	Oxygen during the night rest is accompanied by reduction of the biomarker NTproBNP (pg/mL). Oxygen during the night rest is accompanied by reduction the biomarker TnThs (pg/mL).	To analyze if the treatment with oxygen during the night rest is accompanied by reduction the biomarkers NTproBNP(pg/mL) and TnThs (pg/mL).	changes from baseline to 6th month
Secondary	Nocturnal oxygen therapy on symptoms using the class function of the NYHA, in the capacity of effort (P6MM).	To assess the benefit of nocturnal oxygen therapy on symptoms using the class function of the NYHA, in the capacity of effort (P6MM).	changes from baseline to 6th month
Secondary	Nocturnal oxygen therapy on symptoms using the class function of the NYHA, in the quality of life (Minnesota score)	To assess the benefit of nocturnal oxygen therapy on symptoms using the class function of the NYHA, in the quality of life (Minnesota score)	changes from baseline to 6th month
Secondary	Nocturnal oxygen therapy on symptoms using the class function of the NYHA, in the quality of the dream (pittsburg score).	To assess the benefit of nocturnal oxygen therapy on symptoms using the class function of the NYHA, in the quality of the dream (pittsburg score).	changes from baseline to 6th month