Condition category
Surgery
Date applied
14/04/2020
Date assigned
13/05/2020
Last edited
13/05/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Patients with pre-existing lung conditions undergoing heart surgery are at higher risk of complications after surgery such as chest infection or pneumonia. They may need a tight-fitting mask to help them breathe and ensure that enough oxygen gets into their blood and carbon dioxide is removed. This treatment is costly, labour intensive and can be uncomfortable. Treatment for lung complications can lead to a prolonged hospital stay or even death. Recently, there has been increased interest in the use of high-flow nasal therapy (HFNT) after cardiac surgery. High-flow nasal therapy (HFNT) provides warmed humidified oxygen (air that is warmed and contains some moisture) and has been shown to assist breathing and improve patient recovery. HFNT is comfortable during use and may be even more comfortable than standard treatment with dry oxygen via a face mask or nasal prongs. Without a tight-fitting mask, patients can eat normally and speak freely. In light of this, a study recently investigated whether high-risk patients with certain lung conditions (asthma, chronic obstructive pulmonary disease) or a risk factor for postoperative lung complications (obesity, recent chest infections or heavy smoking), would benefit from routine administration of high-flow nasal therapy immediately after cardiac surgery. The study showed that when compared with standard care, the use of HFNT significantly reduced hospital length of stay (by 29%) and was associated with fewer re-admissions to the intensive care unit. This was the first randomised trial to examine the effect of high-flow nasal therapy compared to standard dry oxygen via nasal prong, on patient-relevant outcomes (length of hospital stay), after open-heart surgery in patients at high risk of postoperative lung complications. The researchers presented the study results to patients who participated in this first trial and both clinicians and participants agreed that it is extremely important to test whether the results can be replicated in a large multicentre study. This study will expand the first trial into nine other UK hospitals (ten hospitals in total including Royal Papworth Hospital), in order to see if the positive findings can be repeated and whether HFNT should become routine in this patient group after cardiac surgery.

Who can participate?
Patients aged 18 or over who are scheduled to undergo open-heart surgery and have one or more risk factors (e.g. chronic lung disease [COPD], asthma, current or recent smoker, recent chest infection, obesity) for developing breathing complications after the operation.

What does the study involve?
To assess the effect of HFNT the researchers will be recruiting a minimum of 850 participants from ten UK hospitals and randomly allocating them to receive high-flow nasal therapy or standard oxygen therapy. Before their surgery, participants will be asked to complete two quality of life questionnaires and a questionnaire collecting information about where they live, health service use 1 month before surgery and current medications. On the day of surgery, the surgical procedure will go ahead as usual and it will be during surgery that allocation to treatment is done. As participants are woken from surgery, the intensive care nurses and doctors will give the allocated therapy for a minimum of 16 hours after surgery. Upon discharge from hospital, participants will be asked to maintain a location and medication diary and to complete the same questionnaires as before surgery, on three further occasions. Participants will be followed up by the Royal Papworth Hospital research team at 30 and 90 days after surgery.

What are the possible benefits and risks of participating?
High-flow nasal therapy is an established therapy which is proven to be safe and effective in a variety of clinical settings. If, after surgery, participants require more support with their breathing, the clinical team will always have the ability to give what they feel is most beneficial. High-flow nasal therapy does generate some low-level noise and participants may feel hot whilst wearing the device due to the warmed humidified oxygen. If a participant starts to feel too hot, a nurse or doctor can decrease the temperature of the oxygen slightly or provide a fan to cool them down. There are no direct personal benefits for participating in the study; however, participants could help a future generation of patients make better-informed choices about their treatment. For participants allocated to high-flow nasal therapy, they may experience benefits in terms of making breathing easier, reducing the chances of their lungs getting blocked by secretions and reducing the chances of picking up a chest infection (e.g., pneumonia). This may mean participants feel better quicker after surgery.

Where is the study run from?
Royal Papworth Hospital (UK)

When is the study starting and how long is it expected to run for?
January 2019 to September 2023

Who is funding the study?
National Institute for Health Research, Health Technology Assessment (NIHR HTA) (UK)

Who is the main contact?
The NOTACS Team
papworth.notacsstudy@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Prof Andrew Klein

ORCID ID

Contact details

Chief Investigator
Royal Papworth Hospital NHS Foundation Trust
Papworth Road
Cambridge Biomedical Campus
Cambridge
CB2 0AY
United Kingdom
+44 (0)1223 639 349
andrew.klein@nhs.net

Type

Scientific

Additional contact

Miss Melissa Earwaker

ORCID ID

Contact details

Royal Papworth Hospital NHS Foundation Trust
Papworth Road
Cambridge Biomedical Campus
Cambridge
CB2 0AY
United Kingdom
+44 (0)1223 639 712
melissa.earwaker@nhs.net

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 45298, IRAS 278290

Study information

Scientific title

Nasal high-flow oxygen therapy after cardiac surgery (NOTACS) study: effect of high-flow nasal therapy on patient-centred outcomes in patients at high risk of postoperative pulmonary complications after cardiac surgery: a multicentre randomised controlled trial

Acronym

NOTACS

Study hypothesis

To determine if prophylactic use of HFNT (for a minimum of 16 hours after tracheal extubation) is clinically- and cost-effective up to 90 days after surgery, for adult patients undergoing cardiac procedures with cardiopulmonary bypass who are at high risk of postoperative pulmonary complications.

Ethics approval

Approved 24/04/2020, Yorkshire & The Humber - Leeds West Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, UK; +44 (0)207 1048 088; leedswest.rec@hra.nhs.uk), REC ref: 20/YH/0133

Study design

Randomised; Interventional; Design type: Treatment, Device

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Postoperative pulmonary complications after cardiac surgery

Intervention

The study is an adaptive, multicentre, parallel-group, randomised controlled clinical trial with embedded cost-effectiveness analysis comparing the use of high flow nasal therapy (HFNT), to standard oxygen therapy for a minimum of 16 hours after tracheal extubation, in patients at high risk of respiratory complications following cardiac surgery. Participants will be recruited over 3 years. Potential participants scheduled for elective or urgent first time or re-do cardiac surgery (coronary artery bypass grafting (CABG), valve surgery or both) will be screened for eligibility. Written informed consent will be obtained from all research participants prior to any study-related procedures. Baseline quality of life questionnaires will be completed. Randomisation will be performed while the participant is undergoing surgery. Participants will be randomly assigned to receive either HFNT or standard oxygen therapy using an online tool (provided by Sealed Envelope). Randomisation will be stratified by centre. After cardiac surgery, participants will be transferred sedated and with their trachea intubated to the post-surgical recovery area. This may be an Intensive Care Unit, High-Dependency Unit or specific Recovery Unit as per local practice. Once participants fulfil the standard agreed protocol [minimal bleeding via chest drains; temperature > 36°C; stable cardiovascular function; neuromuscular block worn off or reversed; sedation stopped; patients responsive to command and successful trial without mechanical ventilation (defined as oxygen saturation (Sp0₂)> 93% with inspired oxygen less than or equal to 60%)], they will then be extubated according to the agreed Trial Extubation Protocol (Appendix 2 in the protocol) and will receive either HFNT or standard oxygen therapy for a minimum of 16 hours according to their randomised allocation. Participants will be transferred to the surgical ward as per local practice and will be assessed at least every 24 hours as per local practice – if Sp0₂ > 93% on air and RR < 20, then HFNT or standard oxygen will be discontinued. If Sp0₂ <93% or RR > 20, then HFNT or standard oxygen will be continued for a further 24 hours then the participants will be re-assessed every 24 hours. If a participant deteriorates during HFNT or standard oxygen therapy, then the agreed Trial Escalation of Respiratory Therapy Protocol will be followed (Appendix 3 in the protocol). At discharge participants will complete the quality of life questionnaires again and be given a patient location and medication diary to complete up to 90 days after surgery. Participants will be asked to record any changes to their living location and also any changes to their medication after surgery. Participants will be also followed up by the central clinical trials unit staff and contacted at 30 and 90 days to collect outcome data and complete questionnaires (all by internet or phone, no additional visits to the hospital necessary). Participants will be asked at the time of recruitment if they would like to use online questionnaires or telephone to collect data. GPs or their receptionists will be contacted by the central clinical trials unit staff to verify data collected. Participants will normally attend back to the hospital for surgical follow-up at 6-8 weeks independently of the trial.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Number of days at home in the first 90 days after surgery, measured by the Patient Location and Medication Diary at 90 days
2. Health economic analysis to estimate the incremental cost-effectiveness and cost-utility of HFNT versus standard oxygen therapy, measured using Patient and Family Resource Use Questionnaires at baseline, discharge, 30 and 90 days

Secondary outcome measures

The following are exploratory secondary outcomes of the study:
1. Estimates of the incremental cost-effectiveness and cost-utility of HFNT versus standard oxygen therapy, calculated by a health economic analysis at 30 days
2. Mortality measured by the incidence of death reported from patient follow-up and medical records at 30 and 90 days.
3. Incidence of postoperative pulmonary complications measured using medical notes during primary admission to hospital
4. ICU re-admission rate measured using the in-patient diary eCRF at any time during primary hospital admission
5. Length of ICU stay (days) measured using the in-patient diary eCRF during primary hospital admission
6. Length of hospital stay (days) measured using the in-patient diary eCRF during primary hospital admission
7. Incidence of stroke measured from patient follow-up and medical records at 30 and 90 days
8. Incidence of sepsis measured from patient follow-up and medical records at 30 and 90 days
9. Incidence of myocardial infarction measured from patient follow-up and medical records at 30 and 90 days
10. Oxygenation measured by ROX Index (defined as Sp0₂/Fi0₂ to respiratory rate ratio) at 2, 6, 12, 24 and 48 hours post-extubation
11. Patient-reported outcomes measured using the EQ-5D-5L questionnaire at baseline, discharge, 30 and 90 days
12. Patient level of assistance needed with activities of daily living, measured using the BARTHEL questionnaire at baseline, discharge, 30 and 90 days
13. Quality of survival measured using EQ-5D-5L Quality Adjusted Life Years (QALYs) at baseline, discharge, 30 and 90 days
14. Health service and resource use measured using Patient and Family Resource Use Questionnaires at baseline, discharge, 30 and 90 days

Overall trial start date

01/01/2019

Overall trial end date

01/09/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged 18 years or over
2. Undergoing elective or urgent first-time or redo cardiac surgery (CABG, valve surgery, surgery on the aorta or any combination)
3. Have one or more clinical patient-related risk factor for postoperative pulmonary complications (COPD, asthma, lower respiratory tract infection in last 4 weeks as defined by use of antibiotics, body mass index > = 35 kg/m², current (within the last 6 weeks) heavy smokers (> 10 pack years)

For the purposes of the study, the following definitions apply:

Asthma is a disease characterized by recurrent attacks of breathlessness and wheezing, and patients will have been prescribed medication by inhalers or nebulisers (either bronchodilators or steroids).

Chronic Obstructive Pulmonary Disease (COPD) is an umbrella term used to describe chronic lung diseases that cause limitations in lung airflow. The more familiar terms 'chronic bronchitis' and 'emphysema' are no longer used but are now included within the COPD diagnosis. The most common symptoms of COPD are breathlessness, or a 'need for air', excessive sputum production, and a chronic cough. Patients suitable for the NOTACS study will have been prescribed medication by inhalers or nebulisers (either bronchodilators or steroids).

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 850; UK Sample Size: 850

Participant exclusion criteria

1. Requiring home oxygen therapy
2. Deep hypothermic circulatory arrest planned
3. Contraindication to HFNT, e.g. nasal septal defect
4. Requirement for home respiratory support (including: CPAP, BiPAP)
5. Requiring emergency cardiac surgery defined as surgery required within 24 hours of the decision to operate
6. Patients not fluent in English

Recruitment start date

01/09/2020

Recruitment end date

01/06/2023

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Papworth Hospital NHS Foundation Trust
Papworth Everard
Cambridge
CB23 3RE
United Kingdom

Trial participating centre

Blackpool Teaching Hospitals NHS Foundation Trust
Victoria Hospital Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom

Trial participating centre

University Hospitals Of Leicester NHS Trust
Leicester Royal Infirmary Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
4th Floor, Gassiot House St Thomas's Hospital Westminster Bridge Road
London
SE1 7EH
United Kingdom

Trial participating centre

Royal Brompton & Harefield NHS Foundation Trust
Royal Brompton Hospital Sydney Street
London
SW3 6NP
United Kingdom

Trial participating centre

South Tees Hospitals NHS Foundation Trust
James Cook University Hospital Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital Mindelsohn Way Edgbaston
Birmingham
B15 2GW
United Kingdom

Trial participating centre

The Royal Wolverhampton NHS Trust
New Cross Hospital Wolverhampton Road Heath Town
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

King's College Hospital NHS Foundation Trust
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

NHS National Waiting Times Centre Board
Agamemnon Street
Clydebank
G81 4DY
United Kingdom

Sponsor information

Organisation

Royal Papworth Hospital NHS Foundation Trust

Sponsor details

c/o Ian Smith
Papworth Road
Cambridge Biomedical Campus
Cambridge
CB2 0AY
United Kingdom
+44 (0)1223639715
ian.smith38@nhs.net

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR128351

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

1. The researchers will publish the protocol in a journal
2. Planned publication in a high-impact peer-reviewed journal

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/09/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

14/04/2020: Trial's existence confirmed by the NIHR.