Replication of the D58 Asthma Trial in Healthcare Claims Data

Completed

• Conditions: Asthma
• Interventions: Drug: Budesonide-Formoterol; Drug: Budesonide

• Registration Number: NCT04892732
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Detailed Description

This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Study Timeline

• Study Start: 2020-10-29
• Study First Submitted: 2021-05-14
• Study First Submitted QC: 2021-05-14
• Study First Posted: 2021-05-19
• Primary Completion: 2021-06-11
• Study Completion: 2021-06-11
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-25
• Last Update Posted: 2023-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66581

Inclusion Criteria

• ≥12 years of age

• Documented clinical diagnosis of asthma for ≥1 year prior to randomization

• History of at least one asthma exacerbation in the previous year (but none in the 4 weeks prior to randomization. An asthma exacerbation was defined as an event requiring treatment with systemic corticosteroids or requiring hospitalization (i.e. an inpatient stay or >24-hour stay in the observation area of an emergency room or local equivalent)

• Receiving either:

  1. A stable dose of ICS alone or in combination with a LABA, leukotriene receptor antagonist or other maintenance therapy/therapies for ≥4 weeks prior to randomization (any patient maintained on a stable high-dose ICS with or without a LABA or LTRA or other maintenance therapy/therapies was required to have an ACQ6 total score of <1.5 at screening) OR
  2. A stable dose of LTRA or xanthine monotherapy (for ≥4 weeks prior to randomization) or daily SABA (in the 4 weeks before randomization but ≤8 puffs a day on two consecutive days, or ≥25 puffs in one day, in the 7 days prior to screening). Patients on LTRAs, xanthines, or daily SABA, were eligible only if they recorded an ACQ6 total score of ≥1.5, and in the investigator's clinical judgment, the patient's asthma severity could have justified treatment with ICS or ICS/LABA combination

Exclusion Criteria

• A history of life-threatening asthma (defined as an asthma episode that required intubation and/or was associated with hypercapnia requiring non-invasive ventilatory support)

• One of the following:

  1. Any asthma exacerbation requiring systemic corticosteroids within 4 weeks prior to randomization OR
  2. >4 separate exacerbations OR
  3. >2 hospitalizations (an inpatient stay or >24- hour stay in the observation area of an emergency room or local equivalent) due to asthma in the previous year

• Received systemic corticosteroids for any reason in the 4 weeks prior to randomization

• Had an ongoing asthma exacerbation requiring systemic corticosteroids

• Concurrent respiratory disease (chronic obstructive pulmonary disease, chronic bronchitis, emphysema, idiopathic pulmonary fibrosis, bronchiectasis, and/or any pulmonary disease)

• A smoking history of >10 pack-years

• Respiratory infection or other viral/bacterial illness

• Pregnancy (current/planned) and lactation

• Malignancy (with the exception of basal cell carcinoma) within the 5 years prior to study commencement

• Omalizumab or any other monoclonal/polyclonal antibody use in the 6 months prior to randomization

• Concomitant β-blocker use

• Drug/alcohol abuse

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Budesonide-formoterol	Budesonide-Formoterol	Exposure Group
Budesonide	Budesonide	Reference Group

Primary Outcome Measures

Name	Time	Method
First serious asthma-related event	Through study completion (a median of 88-116 days)	A composite of adjudicated death, intubation, and hospitalization

Secondary Outcome Measures

Name	Time	Method
Asthma-related hospitalization	Through study completion (a median of 88-116 days)
Asthma-related intubation	Through study completion (a median of 88-116 days)
Asthma-related death	Through study completion (a median of 88-116 days)

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States