A Phase IV, Drug Utilization Surveillance Study to Assess the Clinical Impact of Digital Dose Counter pMDIs On Bronchial Asthma Control: DUSS Analyses (Preprint)
Authors:   DUSS Investigators
Published: February 2019

BACKGROUND

Asthma control with Persistent symptoms in India remains a clinical enigma with likely incriminating factors including Non- &/or Pseudo-adherence to the ICS/LABA. USFDA guidance recommends the use of dose-counter pMDIs with further mechanisms to track Adherence & Pseudoadherence in real-world settings

OBJECTIVE

Digital dose counter pMDIs offers simplified reliable tracking of individual ‘actuated’ dosages with ‘END’ display at the completion of labelled therapeutic aerosol spray. The translational impact on Symptom persistence with likely unwarranted exposure to ‘Step up’ strategy is often prevented if not treated as in these cases of ‘Pseudo’ Severe Asthma .To further assess the real-world acceptance and clinical impact of Digital dose-counter pMDIs, in Bronchial asthma including Poorly or Uncontrolled bronchial asthma cases, an non-interventional, observational study was planned.

METHODS

A national, retrospective, case cohort analyses as Drug Utilization Surveillance study for Digital pMDIs in Br. asthma was conducted in Sept ’16 for outpatient settings of India. The retrospective analyses was initiated and conducted as per ICH GCP principles and Declaration of Helsinki following study protocol and documents approval by local Ethics committee approval with subsequent Clinical Trial Registry of India registration.

RESULTS

Consecutive cases of Moderate to Severe asthma with uncontrolled status (n=4575) with baseline and follow-up status for at least one GINA symptom assessment score on Digital dose-counter pMDIs from 500 centers across India were available for analyses. Asthma control was assessed as Partly (4575) and Uncontrolled status (2942) cases respectively. Per protocol analyses for Uncontrolled Asthma control group evaluated by GINA symptom assessment score was further assessed for Well controlled status at 8th week in 92.7 % cases (2727/2942) for above group. Adverse events (106, 2%) of mild to moderate intensity were reported. Nebulization was required in two cases with episodic breathlessness and discharged with no consequent sequelae. Post hoc analyses for baseline poorly controlled cases who ‘Switched’ exclusively on Digital dose-counter pMDIs monotherapy or combination with Xanthines or LAMAs showed ‘Well control’ asthma status of 85.9% (p=0.044) , 95.4% (p=0.048), 80.3% (p=0.28). The patient acceptability criteria for ‘Empty’ canister well correlated with the clinical strategy to identify and avoid Pseudoadherence in baseline poorly controlled or difficult –to- treat asthma cases especially in the patients who ‘Switched’ exclusively to Digital pMDIs (582) demonstrating responses viz. ‘Use till Twenty dose display’ (41.6%, ‘Use till END display (53.2%), ‘Use till LAST spray’ (5.1%)

CONCLUSIONS

Digital pMDIs offers Simple, accurate & reliable tracking of Non- & Pseudoadherence while highlighting incremental Asthma control rates in Severe or Pseudo-Severe Asthma cases before risk assessment for further ‘add-on’ therapy

CLINICALTRIAL

Registration CTRI/2018/06/014595