Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Validation of a Predictive Score for HAST

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03728595
Recruitment Status : Unknown
Verified March 2019 by The Leeds Teaching Hospitals NHS Trust.
Recruitment status was:  Recruiting
First Posted : November 2, 2018
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
The Leeds Teaching Hospitals NHS Trust

Tracking Information
First Submitted Date October 31, 2018
First Posted Date November 2, 2018
Last Update Posted Date April 1, 2019
Actual Study Start Date October 29, 2018
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 1, 2018)
ROC AUC for Model 1 (3*SaO2 - HCO3 - 4 if ILD - 4 if F -3 if COPD), and the relative sensitivity, specificity, positive and negative predictive value of the threshold identified for negative and positive HAST [ Time Frame: Up to 36 months ]
The score based on Model 1 will be computed for all subjects and ROC curve analyses will be used to assess predictive value. Sensitivity, specificity, PPV and NPV for criteria previously identified in a historic cohort will be assessed.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: November 1, 2018)
  • ROC AUC for the simplified score (3*SpO2 - sHCO3 - 4 if ILD - 4 if F - 3 if COPD) [ Time Frame: Up to 36 months ]
    The simplified score will be computed for all subjects. ROC analyses will be performed and criteria to identify negative and positive HAST at 95%, 97.5% and 99% will be chosen.
  • ROC AUC for Model 2, and Model 3 and for baseline pO2 and relative sensitivity, specificity, positive and negative predictive value of the previously identified thresholds. [ Time Frame: Up to 36 months ]
    The scores based on Model 2 and 3 will be computed for all subjects and ROC curve analyses will be used to assess predictive value. Sensitivity, specificity, PPV and NPV for criteria previously identified in a historic cohort will be assessed.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 1, 2018)
  • Negative and positive predictive value for the criteria chosen for the simplified score. [ Time Frame: Up to 36 months ]
    Criteria to maximise specificity for negative and positive HAST, respectively, will be chosen for the simplified score (Outcome 2). NPV and PPV for these criteria will be assessed.
  • Identification of a new predictive model for the outcome of the HAST [ Time Frame: Up to 36 months ]
    Exploratory outcome: in case the previously identified models will not be validated, a new score will be developed using binary logistic regression analysis.
  • Identification of a model to predict the flow-rate of oxygen required by patients who have a positive HAST. [ Time Frame: Up to 36 months ]
    During the HAST flow-rate of oxygen is titrated for patients with a positive outcome. As exploratory outcome we aim to develop a model to predict the final flow-rate required for patients who need oxygen in flight.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Validation of a Predictive Score for HAST
Official Title A Predictive Score to Reduce the Use of Hypoxic-altitude Simulation Test (HAST) in Patients With Chronic Respiratory Disease Planning Air Travel - an External Validation Prospective Study
Brief Summary

Patients with chronic lung diseases travelling by plane often suffer with symptoms related to lower oxygen levels they are exposed to while flying.

Therefore, patients with respiratory conditions are routinely assessed to establish if they need supplemental oxygen in flight. A hypoxic altitude simulation test (HAST) is often part of this assessment and consists in having patients breathe a oxygen/nitrogen blend with a lower oxygen concentration compared to normal room air, simulating in-flight conditions. Oxygen levels are measured before and after the test through a blood sample (from the earlobe or an artery in the wrist) and with a finger probe. In-flight oxygen is required if the oxygen level in the blood is lower than 6.6 kPa. HASTs are time consuming, costly, and require a dedicated hospital appointment.

Using historical data, the Investigators developed scores based on capillary blood gas (blood sample from the earlobe), diagnosis and sex to predict the outcome of the HASTs. The Investigators validated the proposed scores in a separate historic cohort of patients and showed it had good concordance with the HASTs results.

In this study, the Investigators want to confirm prospectively if the score, based on blood results (venous and/or earlobe), can predict the outcome of the HASTs and therefore reduce the number of tests performed, travel time for patients, and costs for the NHS.

All patients, aged 18 or older, who are having a HAST for clinical purposes at the cardio-respiratory lab at Leeds Teaching Hospital NHS Trust will be invited to take part in the study. The Investigators will record diagnosis, results of HAST and previous spirometry from the medical notes, perform a spirometry if not done in the previous 12 months and collect a blood sample (one tube, 4 mls). With these data, the Investigators will calculate the score and assess its agreement with the outcome of the HAST.

Each participant's involvement in the study will last for approximately 90-120 minutes, which is the normal duration of a HAST.

The Investigators aim to include up to 280 subjects in the study.

Detailed Description

Over the last two decades, there has been a significant increase in the number of people flying on a regular basis. As a result, more individuals with chronic respiratory disease are being referred for formal assessment to assess if they require inflight oxygen.

At cruising altitude, passengers are exposed to reduced atmospheric pressure equivalent to an altitude of 8000 ft, corresponding to a reduction of oxygen from 21% to approximately 15%. National and International recommendations on air travel suggest screening patients with chronic lung diseases for the need of in-flight oxygen supplementation. However, due to the paucity of available evidence, there is no consensus on which investigation should be performed and the precise risk factors associated with in-flight complications.

The British Thoracic Society, which published the most recent and comprehensive recommendations on this topic, recommends that patients with respiratory diseases should be assessed clinically, and in specific situations, a hypoxic altitude simulation tests (HAST) should be performed. Unfortunately, the vast majority of these recommendations are level C at best, as current evidence is limited to a handful of prospective or retrospective analyses.

A standard hypoxic altitude simulation test requires the patients to breathe a blend of 15% oxygen in nitrogen for 20 minutes. This simulates the oxygen tension at 8000 ft, the equivalent cabin pressure. Blood gas measurements are taken before and after the test. A fall in the pO2 below 6.6 kPa is considered indicative for use of in-flight oxygen.

Often the HASTs yield negative results (i.e. no inflight oxygen required). These tests are heavy on resources, time consuming, costly, not widely available and require dedicate hospital appointment. Thus, predictors of outcomes of HASTs are needed to reduce the number of HASTs performed.

Several studies have looked at predictors of oxygen desaturation during HAST in varying populations with the aim of better selecting patients who need the test. However, results have been inconclusive. Data on the role of baseline oxygenation, FEV1 and exercise test in predicting oxygen desaturation during the HAST are conflicting and most studies have been too small to provide decisive answers.

The Investigators recently developed and validate, on historical data, three scores to predict negative HASTs, according to the BTS 2011 recommendations (i.e. scores predicting which patients do not need to undergo a formal assessment). All of these had good ROC AUC and agreement with the outcome of the HAST in the retrospective dataset.

The Investigators hypothesise that the multivariable score (Model 1), based on a combination of CBG variables (bicarbonate and oxygen saturation) and baseline diagnosis (ILD and COPD) would be the best predictor of negative response in a formal HAST. Furthermore, the Investigator hypothesise that the score could be further simplified for the use in clinical practice by measuring the serum bicarbonate and oxygen saturation through a pulse oximeter (Model 1s). This is in light of the good arterio-venous concordance previously demonstrated for bicarbonate and of the good reliability of non-invasive measurement of oxygen saturation. Such a simplified score, if its predictive value is confirmed, would not only reduce the number of unnecessary HAST performed, but also minimise patients' discomfort and hospital appointments, reducing the costs for the NHS.

In this prospective single centre study, the Investigators will assess the validity of the best performing score (Model 1) derived in our retrospective study for negative HAST. In addition, the Investigators want to verify whether the use of SpO2 in place of SO2 and of serum bicarbonate in place of capHCO3 would allow for similar results. The investigators also aim to evaluate the performance of the other predictive scores previously derived in our retrospective analysis, and, if none of these models are a good and effective predictor, we aim to develop a new model based on newly measured data.

The Investigators aim to enroll up to 280 subjects, but interim analyses will be performed with the scope to early terminate the study if primary outcome is met.

Demographic and baseline characteristics of patients will be analysed on the whole population and by the cohorts depending on the underlying diagnosis and the outcome of the HAST.

Receiver operating characteristics (ROC) curves will be plotted to test the hypothesis that the scores are good predictors of negative HASTs. Diagnostic values of the scores will be expressed by sensitivity, specificity, positive and negative predictive values.

Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:

The Investigator will collect a blood sample to be processed for serum bicarbonate.

As processing a sample for serum bicarbonate is very susceptible to pre-analytical sources of error, samples will be analysed immediately after collection and then discarded.

Sampling Method Non-Probability Sample
Study Population Outpatient attending for a HAST at Leeds Teaching Hospital NHS Trust.
Condition
  • Chronic Respiratory Disease
  • Hypoxia, Altitude
  • COPD
  • ILD
  • Cystic Fibrosis
Intervention
  • Diagnostic Test: Venepuncture
    A blood sample will be taken for serum bicarbonate
  • Diagnostic Test: Spirometry
    All patients who have not had a spirometry in the 12 months prior to the HAST will undergo one on the day of the HAST.
  • Diagnostic Test: Hypoxic altitude simulation test (HAST)
    HAST will be performed as per clinical team request. No changes to this intervention will be made for research purposes.
Study Groups/Cohorts Patients with lung disease having HAST

Patients with chronic respiratory diseases who had a hypoxic altitude simulation test (HAST) for clinical purposes will have for research purposes:

  • venepuncture
  • spirometry.
Interventions:
  • Diagnostic Test: Venepuncture
  • Diagnostic Test: Spirometry
  • Diagnostic Test: Hypoxic altitude simulation test (HAST)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: November 1, 2018)
280
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Age ≥18 years old (at the time of HAST)
  • Clinically stable
  • Hypoxic altitude simulation test, scheduled as part of the clinical care

Exclusion Criteria:

  • Inability to provide informed consent
  • Being part of a clinical trial, which would exclude patients who are taking part in other studies including observational studies.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT03728595
Other Study ID Numbers RM18/109075
247902 ( Other Identifier: IRAS )
18/WS/0117 ( Other Identifier: HRA/REC4 West of Scotland )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party The Leeds Teaching Hospitals NHS Trust
Study Sponsor The Leeds Teaching Hospitals NHS Trust
Collaborators Not Provided
Investigators
Principal Investigator: Giulia Spoletini Leeds Teaching Hospital NHS Trust
PRS Account The Leeds Teaching Hospitals NHS Trust
Verification Date March 2019