Award Title: N-Tidal B personal respiratory monitor: an MHRA-notified non-interventional clinical and health economic study with asthma patients to generate the evidence for award of a Class IIB license.
Funder: Department of Health and Social Care

Abstract: This registrational clinical study is an observational, longitudinal study which does not impact on patients' standard care pathways.     A total of 140 patients with poorly-controlled moderate-to-severe asthma will be enrolled at two sites from out-patient asthma clinics, emergency admissions and primary care.  The six-month study duration has been determined to ensure that sufficient asthma exacerbations are captured.     The sample size has been determined to provide an accurate estimate of the sensitivity of the device in predicting exacerbations. It is estimated that up to 60% of exacerbations may be predicted by a  warning signal  from the device based on Tidal Breathing CO2 (TBCO2) change. Assuming a 95% confidence level, it is calculated that 93 exacerbations would be required to obtain an estimate to within ±10% of the true value, which is regarded as an acceptable level for the grant of a Class IIB medical device license. Previously collected data has suggested a mean of 0.79 exacerbations per patient in a six-month period. Thus, to ensure at least 93 exacerbations, a minimum of 117 patients are required.  The total of 140 patients is based on 85% of the patients completing the study.      Patient inclusion criteria are: (i) aged 7 years and over; (ii) a primary diagnosis of asthma; (iii) poorly-controlled asthma, at BTS Treatment Steps 3-5; (iv) patient or parent/legal guardian providing written informed consent. Patients who are unlikely to be able to comply with the requirements of the study or with other respiratory disorders will be excluded.     The study will collect the following from each participant:    Twice-daily short respiratory records of their TBCO2 waveform data for six months  Records of asthma condition and exacerbations according to standard criteria via a phone-based thrice-weekly asthma symptom diary  Clinical reviews and quality-of-life at two-month intervals      On enrolment, patients will undertake a clinical assessment, lung function tests and pulse oximetry for correlation with their initial TBCO2 waveforms. They will also complete quality-of-life questionnaires.  Participants will be provided with an N-Tidal B monitor to capture TBCO2 respiratory records twice-daily at home (morning and evening). Participants will breath normally into the device for a period of 75 seconds. The twice-daily records will identify both within-day and day-to-day variation in TBCO2 waveforms.     Each patient will also visit the study sites at months 2, 4 and 6 (at study end), for clinical assessments, ease-of-use of the device, quality-of-life questionnaires and healthcare resource use.  They will also be assessed by phone when the symptom diary and PEF is suggestive of an asthma exacerbation[References 21], or assessed in hospital if they require oral steroids/hospital admission. A sample of patients/carers will also be interviewed at the end of the study to discuss barriers/enablers to using the device.     The outcomes of this programme will be:    Refined asthma alert algorithm to be incorporated into the N-Tidal B.  Efficacy, safety and technical evidence required for the grant of a Class IIB medical device license.  Clinical papers for publication in respected peer-reviewed medical journals      This study will take 30 months to complete, starting on 1-Nov-2018.

Lay Abstract: Asthma is the most common lung condition, affecting 5.4 million people in the UK. Many people with asthma suffer from breathlessness, chest infections and frequent hospital admissions. Currently, there is no way that people with asthma are able to monitor their condition easily and detect flare-ups early enough to take treatment and avoid going to hospital. As it is hard for people with asthma to know when their lungs are becoming more inflamed and not working as well, it is difficult for them to use their medicines at the right time to manage their asthma well.  As a result, asthma leads to 60,000 emergency hospital admissions each year and results in over 1,400 deaths, the majority of which are avoidable.     We have found that people with asthma breathe out a gas, carbon dioxide (CO2), in a different way to healthy people. The pattern of breathing out CO2 changes further when patients are having a flare-up of their disease. If patients could monitor their CO2, they may recognise when their asthma is getting worse, and take earlier action to avoid flare-ups getting out of hand and going to hospital.     Cambridge Respiratory Innovations Limited is developing a low-cost hand-held device, N-Tidal B, for patients to monitor their asthma at home. This device measures the CO2 pattern when a patient is breathing in and out normally.   In this research, we will provide 140 patients with asthma with a N-Tidal B device. We will ask them to breathe in and out of the device for 75 seconds in the morning and evening for six months, as well as keeping a diary of asthma symptoms, flare-ups and GP or hospital visits. This information will tell us which CO2 patterns best match up with their condition becoming worse, for example having more symptoms of asthma, needing to take stronger asthma medicines or going to hospital. The patients will not be able to see the CO2 pattern, but this information will help us decide which CO2 patterns should provide alerts to patients in the future, so that they can take earlier treatment and possibly avoid emergency visits to hospital. The study has been designed together with a group of patients, who will also design participant information and monitoring study progress.     The results of this study will enable us to obtain approvals for the device to display alerts and to be available to NHS patients. With alerts, the device could help people with asthma detect and predict when they are becoming unwell, enabling earlier treatment, reducing the severity and length of flare-ups, prevent hospitalisation and improve quality-of-life. A device like this which reduces avoidable hospital admissions could save the NHS up to £21 million per year.

Research Activity Codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health Categories: RESPIRATORY