On 7th December 2017 ResMed hosted a HOT-HMV panel in London to discuss the clinical and financial implications of the HOT-HMV trial, the results of which were published in the Journal of the American Medical Association in June 2017.
Chairing the discussion were Professor Mike Morgan and Dr Alice Turner, with presentations from Professor Nick Hart and Dr Patrick Murphy from the HOT-HMV trial team, and also respiratory opinion leaders Professor Anita Simonds and Dr Mark Elliot. The speakers also made up a panel for the audience discussion that followed. Gillian Gibbons, Director at Wychwood Communications, provided this report.
The HOT-HMV trial is the first multi-centre, open label, randomized controlled trial to show that home mechanical ventilation (HMV), combined with home oxygen therapy (HOT), can reduce the risk of hospital readmission in severe COPD patients. Specifically those with an acute COPD exacerbation where there is persisting hypercapnia after discharge. The trial tested the hypothesis that it was beneficial to add the further treatment of HMV to a group of patients with severe COPD for whom there were very limited treatment options.
Dr Murphy outlined the recruitment process in which more than 2000 patients were screened. Of these a third were excluded as they had already had NIV or were at end of life, 11% had high BMI or sleep apnoea and a further 16% didn’t want to take part, while 50% of all patients didn’t meet the persisting hypercapnia requirement.
In terms of the 116 patients that were selected to take part, many had CO2 levels greater than 8KPa, were in late middle age, with a significant number of exacerbations. Most were on LTOT and had significant chronic respiratory failure so it is important to understand that they were very frail patients.
Those selected were randomised into a treatment group receiving both HOT and HMV, and a control group using HOT alone.
It was built-in from the start that if members of the control group breached certain safety criteria, they too would be given HMV. This led to some attenuation of the physiological outcomes in the long-term data – with 29% of the control group crossing to the treatment group, but it was felt that it was not ethical to deny them the treatment.
Clinical Outcomes with the addition of HMV
- Prolonged the median time to readmission from 1.4 months to 4.3 months
- Reduced 28 day readmission by two-thirds
- Exacerbation frequency reduced by a third
- PaCO2 was improved at 12 months
- No detrimental effect on health-related quality of life measures
Clinicians would need to add HMV to HOT in only six patients with the trial’s entry criteria to prevent one readmission to hospital within the following year.
There was no statistically significant effect on mortality – the rate was the same in both groups but it is believed that the mortality effect of the treatment will be delayed. The team are waiting for the three and five year data, and expect to have some figures in the next 12-18 months.
What does it mean for the patient?
The trial clearly demonstrated that the addition of home mechanical ventilation to home oxygen therapy can reduce 12 month readmission rate in selected COPD patients with persistent hypercapnia following a life-threatening exacerbation of COPD. In patient terms this means less time in hospital.
We didn’t just shift exacerbations from the hospital to the home, we actually reduced the exacerbations… on average there was one fewer exacerbation, per patient, per year.
There was also an indication that QOL can also be improved. At six weeks the SRI scale in the treatment group showed a 5.0 difference. This compares with the Australian AVCAL trial where the HROL was reduced and many patients reported being more miserable on the treatment. The results of the HOT-HMV show the QOL as being good or slightly better in the treatment group.
Professor Hart assessed the trial results and concluded that the treatment is clinically effective. He then turned his attention to the health economics and presented a 12-month analysis of using HOT-HMV which has been prepared as an ATS abstract.
This is based on patient level medical resource utilisation (which includes equipment, physician contact and primary and secondary visits) and the QALY outcome.
The results demonstrate that the total patient reported costs within the treatment group were lower than in the control group, driven mainly by reduced primary and secondary care costs. The cost tips into negative territory when you add in procurement of equipment. However the cost per QALY calculation showed a QALY gain at £10,360 that would fall within the remit for NICE funding.
This is based on a 60% probability level, while at 80% probability the QALY cost increases to £30,000. Professor Hart suggests that NICE is now using higher level of cost for patients moving to end of life so this falls within their remit.
The conclusion was that HOT-HIV is a cost effective treatment with clinical benefits in this selected group of patients with hypercapnic COPD.
Will it change clinical practice?
Professor Hart reiterated that when HMV is added to HOT using a high pressure technique, this has been shown to drive down CO2, reduce exacerbation frequency, and reduce readmissions. He believes that if ventilation is used for more than four hours a night, it is likely to improve long-term outcomes and reduce mortality.
The trial results could potentially change clinical practice and improve the way we manage our sickest COPD patients.
Therefore if a patient comes to clinic with a CO2 level greater than 7.0, there should be a prompt to add HMV to HOT.
Dr Elliott discussed the clinical implications of the HOT-HMV trial. He compared the trial with two further studies from Australia and Germany and concluded that to improve quality of life you have to lower the CO2.
What hasn’t been shown yet is whether other COPD patients, who did not fulfill the trial’s entry criteria, could similarly benefit from the addition of HMV to their treatment. One size may not fit all and we need to understand more about the wider application of HMV. It was suggested that the next phase of research should address whether similar benefits are likely in COPD patients outside of the scope of the trial.
Dr Elliott concluded that it has been established that HOT-HMV works but now the work needs to be refined to see how it might operate in practice.
The presentations were followed by a lively debate between the panel and the audience. This addressed a number of issues but the two recurring topics were:
i) The cost-effectiveness and application
There was some concern expressed about the pressures on the community health system and on the long-term management of a high maintenance patient group. This was not an issue that the trial team had experienced as highlighted in the cost analysis but it may be an area that needs further consideration.
ii) Questions around the robustness of the trial.
The HOT-HMV trial demonstrated that there are benefits of using the treatment but the trial population was narrowly defined. This will need to be further refined to understand how it might work for other patient groups. The challenge is to establish who the treatment works for, and more scientific rigor will be required to do this.
So while some questions remain, the discussion has given the incentive to re-evaluate COPD treatment and to consider how they might practically apply HMV.
This is something the trial team has already done. Having taken their findings to the clinical managers at the Lane Fox unit at Guy’s and St Thomas’s Hospital, a COPD Post Acute NIV Pathway is now in place, based on a cost pressure of reducing readmissions by two thirds over the next year. The team will continue to record their findings and the longer outcomes of the patients who participated in the trial.
ResMed was one of the funding providers for HOT-HMV trial. For more information on the trial please visit ResMed.com.