Chronic obstructive pulmonary disease (COPD) causes the progressive deterioration of respiratory function and often leads to intermittent severe exacerbations as the disease advances. Patient outcomes following hypercapnic exacerbations requiring hospitalisation and acute non-invasive ventilation (NIV) are poor, and few treatment options exist for these patients. Exacerbations and hospitalisations also place a significant burden on healthcare systems. The multi-centre, open label, parallel-group, randomised controlled HOT-HMV1 trial investigated the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation (AECOPD) requiring acute NIV. It aimed to identify whether this treatment strategy could improve outcomes for this patient group.
The study recruited severe hypoxic and hypercapnic COPD patients who had been hospitalised for acute decompensated hypercapnic exacerbation of COPD requiring NIV.
116 patients were randomised to two arms: the HOT arm treated with home oxygen therapy (HOT) and the HOT-HMV arm treated with both HOT and home non-invasive ventilation (HMV).
The primary outcome was admission-free survival, a combined endpoint of time to readmission to hospital for any cause or death within 12 months after randomisation. Patients met the primary outcome if they experienced either endpoint.
The recruitment process was designed to ensure that the effect of the therapy was assessed in patients who did not have any significant cause of sleep-disordered breathing and/or respiratory failure other than COPD (e.g. obesity, obstructive sleep apnoea, neuromuscular disease, chest wall disease).
A computer-assisted stratified randomisation was performed to guarantee the balance of the 2 arms of the study with regard to the following factors: age (<65years, ≥65 years); body mass index (BMI) (≤20, >20), current long-term oxygen therapy (yes, no); frequency of COPD-related readmissions during previous 12 months (<3, ≥3); recruitment centre.
Hypoxia and hypercapnia were assessed by blood gas analysis (ABG) 2 to 4 weeks after the resolution of the hypercapnic acidosis to ensure that enrolled patients presented with a chronic condition.
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.
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.
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
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.
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
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
Oxygen therapy (HOT)
Home NIV therapy
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
The HOT-HMV trial has important implications for the clinical treatment of patients with severe COPD and chronic respiratory failure who experience a life-threatening exacerbation.
Wider adoption of home NIV for hypercapnic COPD patients
The HOT-HMV study should prompt changes in the clinical management of severe COPD patients with chronic respiratory failure following a life-threatening exacerbation. This severely ill patient group currently has few treatment options. The results confirm the value of offering home NIV therapy to these patients, a practice already adopted by many expert ventilation centres. They also support the argument that home NIV should be adopted more widely as part of the therapy strategy for severe hypercapnic COPD patients after hospitalisation for AECOPD.
The positive results of the HOT-HMV trial suggest that patients with severe COPD should be systematically screened following a hospitalisation for AECOPD requiring acute NIV to assess their suitability for home NIV therapy.
The HOT-HMV findings confirm the value of the new recommendations provided by the GOLD guidelines. The guidelines now include home NIV as a therapy to consider for the treatment of hypercapnic COPD patients.
HOT-HMV confirms the efficacy and feasibility of using high pressures to treat COPD patients. High pressures were effective in correcting hypoventilation and reducing hypercapnia while QOL assessments and usage statistics indicate that patients tolerated the therapy well.
Home NIV has the potential to reduce the healthcare costs associated with the management of patients with severe COPD. HOT-HMV significantly increased time to hospital readmissions, which place a significant burden on healthcare systems. Reductions in the exacerbation rate also imply that HOT-HMV has the potential to reduce the costs and resources required to treat this group outside hospital.
Furthermore, HOT-HMV may have amplified effects on cost reduction in some systems which apply penalties for recurrent hospital readmissions due to AECOPD.4
* Percentage relative to the total number of excluded patients