Clinical trial NCT03657121: Mortality and Symptom Burden Post Hospitalisation With COPD
Official title: COPD: Comparison of Existing Prognostic Tools for 1 Year Mortality and Assessment of Symptom Burden to Facilitate Advance Care Planning
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Disease, Chronic Obstructive
Pulmonary Disease, Obstructive
Emphysema
Chronic Bronchitis
Chronic Bronchitis With Airways Obstruction
Chronic Bronchitis With Acute Exacerbation
Keywords: Prognosis
Palliative Care
End Stage
Mortality
Palliative
Advance Care Planning
Symptom
Exacerbation
Lead sponsor: Northumbria Healthcare NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: Newcastle-upon-Tyne Hospitals NHS Trust
name: Hospice UK
First posted: 2018-09-04
Enrollment: 447
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Consecutive, unique patients admitted to Northumbria Healthcare NHS Foundation Trust or Newcastle Upon Tyne Hospitals NHS Foundation Trust with an exacerbation of Chronic Obstructive Pulmonary Disease (ECOPD) will be identified and included in the non consenting prognostic study. All eligible patients within this group will be approached to participate in the longitudinal study and will only be included if they consent to do so.

Brief summary: Chronic Obstructive Pulmonary Disease (COPD) is a common progressive lung disease which causes breathlessness and frequent exacerbations, with patients often requiring hospitalisation. Patients with severe COPD commonly become housebound and lose their independence. They have a higher symptom burden than those with incurable lung cancer, yet are less likely to receive specialist palliative care, or to have been engaged in advance care planning (where patients discuss and often document their wishes regarding their future care). Hospital admissions become increasingly common towards the end-of-life; therefore, hospitalisation is a good opportunity to identify patients at risk of poor outcome. Such patients may wish to consider alternatives to admission and avoid intrusive treatments. Unfortunately, predicting which patients are likely to die in the near future is challenging thus far.

The first step required to improve provision of palliative care services, and ensure patients are given the opportunity to make truly informed decisions about their future care, is accurate identification of those most likely to benefit.

Well-designed clinical (prognostic) tools outperform clinician judgement in most settings. The investigators will compare the accuracy of one year mortality prediction of several clinical tools in patients who survive a COPD exacerbation requiring admission. This will initially be performed using existing data collected during previous research (the 1,593 patient validation study for the PEARL score - Previous admissions, extended Medical Research Council Dyspnoea score, Age, Right and Left heart failure), then confirmed in at least 310 patients admitted uniquely and consecutively with an exacerbation of COPD. The latter group of patients will be invited to participate in a longitudinal follow-up study, assessing symptom burden, quality of life, and readmissions over one year.

Detailed description: The PEARL (Previous admissions, Extended Medical Research Council Dyspnoea Score, Age, Right-sided heart failure and Left-sided heart failure) score predicts readmission or death within 90 days of discharge following an exacerbation of Chronic Obstructive Pulmonary Disease (ECOPD), and was developed by the lead supervisor's research team. Within the PEARL derivation cohort (2 hospitals, 824 patients), they have developed a novel tool to predict one year survival. The performance of this novel tool and existing Chronic Obstructive Pulmonary Disease (COPD) prognostic tools will be compared in the PEARL validation cohort (6 hospitals, 1,593 patients). The existing tools are the Body Mass Index, Airflow Obstruction, Dyspnoea and Exacerbations (BODEX) index (score range 0-9); PEARL score (score range 0-9); COPD Gold Standards Framework Prognostic Indicator Guidance (COPD PIG); Comorbidity, Obstruction, Dyspnoea and Exacerbations (CODEX) index (score range 0-10); Age, Dyspnoea and Obstruction (ADO) index (score range 0-14); Dyspnoea, Obstruction, Smoking, Exacerbation (DOSE) index (score range 0-8), the Supportive and Palliative Care Indicators Tool (SPICT) and another tool recently developed by another centre (PubMed reference not yet available). COPD-PIG and SPICT are not scored in the same manner and therefore do not have a range.

Performance of all tools will also be further prospectively assessed in a minimum of 310 patients. The COPD-PIG is intended to only be scored in patients who the clinician "would not be surprised" if they died within one year; the performance of this tool cannot be fully assessed retrospectively. Prospective validation will also allow an assessment of the ease of data collection; this is not available for the existing PEARL cohort but is a key consideration in selection of the final tool to ensure it is appropriate for widespread use on hospital wards. Consecutive, unique patients admitted to Northumbria Healthcare NHS Foundation Trust and Newcastle Upon Tyne Hospitals NHS Foundation Trust with ECOPD will be identified. Demographic and clinical indices, including the components of the nine prognostic tools, will be collected. Caldicott and ethics committee approval are in place (REC:18/NE/0226). Hospital readmissions, utilisation of other healthcare services such as the local palliative care teams and Hospice and survival will be assessed over one year. In common with similar studies, this validation study will be non-consenting.

Patients identified as high-risk by the selected tool who survive beyond one year may still warrant palliative care input if their symptom burden is high. The patients enrolled in the validation study will be invited to participate in a consenting longitudinal outcomes study, aiming for at least 50% participation. Symptom burden and functional status will be assessed using the St George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Score (HADS), Australian modified Karnofsky Score (AKPS), Extended Medical Research Council Dyspnoea (eMRCD) score, and modified Borg scale at baseline, and 1, 3, 6 and 12 months. The baseline and 3 month assessments will be conducted via face to face meetings. The additional 1, 6 and 12 month assessments will be conducted over the phone. This data will be used both to calculate the relationship between symptom burden and death, and to identify the characteristics of patients who are especially symptomatic.

The characteristics of the cohort will be summarised using standard descriptive statistics appropriate to the level and distribution of the data. Groups will be compared (including by mortality outcome) using standard tests of statistical inference (e.g. t-test, Mann-Whitney U test, Fishers exact test). The performance of candidate prognostic tools will be compared by 1) assessing the positive and negative predictive value within the high-risk and low risk groups respectively; and 2) Area Under the curve of the Receiver Operating Characteristic (AUROC) analysis, with performance compared using the method of DeLong et al. Where data imputation is required, this will be done using multiple imputation methods. Statistical significance will be set at 5% throughout. The statistical analysis plan will be finalised prior to end of recruitment to avoid potential bias.

Eligibility criteria: Inclusion Criteria:

1. Age 35 years or older.
2. Smoking history greater than or equal to 10 pack years.
3. Obstructive spirometry (FEV1/FVC \< 0.7).
4. ECOPD primary diagnosis.
5. Survival to discharge.

Exclusion Criteria:

1. Previous inclusion in the study.
2. Malignant neoplasm or other pathology likely to limit survival to less than 1 year.
3. For the longitudinal study only, inability to give informed consent.

Primary outcomes:
measure: Positive predictive value of the prognostic tools listed for prediction of one year mortality.
timeFrame: 12 months
measure: Sensitivity of the prognostic tools listed for prediction of one year mortality.
timeFrame: 12 months
Secondary outcomes:
measure: Ease of completion of prognostic tools assessed by Likert scale
timeFrame: 12 months
measure: Ease of completion of prognostic tools assessed by missing data.
timeFrame: 12 months
measure: For each prognostic tool, the area under the receiver operating characteristic curve.
timeFrame: 12 months
measure: Negative predictive value of the prognostic tools for prediction of one year mortality.
timeFrame: 12 months
measure: Hospital readmission rates at 30, 90 and 365 days.
timeFrame: 12 months
measure: Proportion of patients on the palliative care register and relation to mortality.
timeFrame: 12 months
measure: Utilisation of palliative care services: hospice; community palliative care team.
timeFrame: 12 months
measure: Inter-observer agreement on scoring of the prognostic tools
timeFrame: 12 months
measure: Determine baseline St George's Respiratory Questionnaire score
timeFrame: 12 months
measure: Determine baseline Hospital Anxiety and Depression Score
timeFrame: 12 months
measure: Determine baseline modified Borg score
timeFrame: 12 months
measure: Assess baseline Australia-modified Karnofsky Performance Status
timeFrame: 12 months
measure: Mean change in SGRQ compared to MCID.
timeFrame: 12 months
measure: Mean change in HADS compared to MCID.
timeFrame: 12 months
measure: Mean change in modified BORG score compared to MCID.
timeFrame: 12 months
measure: Mean change in AKPS compared to MCID.
timeFrame: 12 months
measure: Duration SGRQ score maintained above baseline.
timeFrame: 12 months
measure: Duration HADS score maintained above baseline.
timeFrame: 12 months
measure: Duration modified BORG score maintained above baseline.
timeFrame: 12 months
measure: Duration AKPS maintained above baseline.
timeFrame: 12 months
measure: Relation between clinically significant anxiety on discharge and survival.
timeFrame: 12 months
measure: Relation between clinically significant depression on discharge and survival.
timeFrame: 12 months
measure: Relation between clinically significant anxiety on discharge and quality of life.
timeFrame: 12 months
measure: Relation between clinically significant depression on discharge and quality of life.
timeFrame: 12 months
measure: Relation between clinically significant anxiety on discharge and functional status.
timeFrame: 12 months
measure: Relation between clinically significant depression on discharge and functional status.
timeFrame: 12 months
measure: Relation between clinically significant anxiety on discharge and readmissions.
timeFrame: 12 months
measure: Relation between clinically significant depression on discharge and readmissions.
timeFrame: 12 months
measure: Best prognostic tool to predict poor QoL and/or death within one year, as per positive predictive value and sensitivity.
timeFrame: 12 months
Other outcomes:
Locations:
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle Upon Tyne Hospitals NHS Foundation Trust
state: Tyne And Wear
city: Cramlington
country: United Kingdom
facility: Northumbria Healthcare NHS Foundation Trust
Study officials:
affiliation: Northumbria Healthcare NHS Foundation Trust
name: Sarah M Gillespie, MBChB
role: PRINCIPAL_INVESTIGATOR
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