64 patients completed the 12-month study period (28 in the HOT group, 36 in the HOT-HMV group).
All primary and secondary analyses were undertaken on the intention-to-treat principle.
51% reduction in risk of hospital readmission or death within 12 months
There was a 51% reduction in the risk of hospital readmission or death in the HOT-HMV arm compared to the HOT arm. Median admission-free survival time was 4.3 months in the HOT-HMV arm compared to 1.4 months for those in the control group. This translates to an increase of over 90 days in the median time to first event for the HOT-HMV arm.
17% absolute risk reduction
The risk of hospital readmission or death at the end of the 12 months was 63.4% in the HOT-HMV group and 80.4% in the HOT group, meaning an absolute risk reduction of 17% (95% CI, 0.1%-34.0%). This translates to a need to treat 6 patients to avoid one hospital readmission or death in 12 months.
Given the significant cost of hospital admissions for severe COPD, this implies that HOT-HMV could help to reduce the economic burden of this disease.2
Positive results driven by hospital readmission
These results were driven by a reduction in hospital readmission. There were no statistically significant differences in mortality at 12 months or for the event triggering the primary outcome.
It should be noted that the study was not powered to detect differences in mortality outcomes.2
In addition, a post-hoc analysis showed that in the first 28 days after randomisation there was a 74% reduction in the risk of hospital readmission for those in the HOT-HMV arm. Two-thirds fewer readmissions were observed in this period in this patient group compared to the HOT group.
Exacerbation rate reduced by 34%
In addition to the positive effect on time to first readmission or death, further analysis showed that the exacerbation rate over 12 months was reduced by 34% in the HOT-HMV arm.
This suggests that patients receiving HOT-HMV may experience better outcomes.2
QOL maintained and therapy well tolerated
Health-related quality of life for patients in the HOT-HMV arm was significantly higher at 6 weeks according the results of the Severe Respiratory Insufficiency (SRI) questionnaire and at 3 months according the results of the St George’s Respiratory Questionnnaire (SGRQ).
These benefits became less marked over time, with no statistically significant difference thereafter.
HMV usage increased from a median of 4.7 hours per night at 6 weeks to 7.6 hours at 12-month follow up.
These results indicate that the high-pressure ventilation strategy was well tolerated.
The therapy was well tolerated and QOL was maintained despite the use of high pressures. Hours of use increased over the course of the study, possibly because patients felt it was alleviating their symptoms.2
The modest effect on QOL is unsurprising: the patient population had severe disease and high levels of physical impairment at baseline. After the first 3 months, there was a dilution of treatment effect as 18 patients from the HOT group were allowed to receive the ventilation therapy, in line with study protocol.2
Therapy initiation and settings
Oxygen therapy (HOT)
- Both groups received HOT.
- Oxygen was started in both arms, at the lowest flow rate required to increase PaO2 above 60mmHg without producing a decompensated respiratory failure.
- Both arms received a median of 1 litre/minute of oxygen.
Home NIV therapy
- The HOT-HMV arm received HMV in addition to HOT.
- The study used a high-pressure ventilation strategy.
- In-patient NIV titration was performed during the night after a daytime acclimatisation, and with O2 therapy set at daytime flow rate.
- Inspiratory pressure was initially set at 18 cmH2O and was titrated to the highest level tolerated by the patient under SpO2 and tcCO2 monitoring, reaching a median IPAP of 24 cmH2O.
- The back-up rate was moderate (median 14 bpm), as high rates have not been found to be beneficial in previous trials.
Home NIV effectively corrected hypoventilation and reduced CO2 level
Mean / Max tcCO2
Significant improvements were observed in nocturnal mean tcCO2 and maximum tcCO2 in the HOT-HMV arm showing that ventilation therapy was effective in correcting hypoventilation.
HMV therapy was effective in reducing daytime levels of CO2, as measured by ABG. Patients receiving HOT-HMV obtained a statistically significant benefit at 6 weeks and 3 months.
The dilution in the therapy effect on TcCO2 and PaCO2 can be explained by the 18 patients from the HOT group who required and were permitted to receive ventilation therapy.2