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Sputum Cytometry Guided Management for the Elimination of Chronic Cough in Patients With ILD

Not Applicable
Not yet recruiting
Conditions
ILD
Interventions
Other: Sputum-guided management
Other: Standard of Care
Registration Number
NCT05086432
Lead Sponsor
McMaster University
Brief Summary

In Interstitial Lung Disease (ILD) there is thickening of lung tissue, which makes it difficult for patients to breathe and get enough oxygen into their bodies. In addition to shortness of breath, daily cough is very common, with 4 out of 5 patients experiencing this symptom. Cough in particular has a major impact on the ability to exercise, be active, and to simply enjoy life.

There are many reasons for cough in ILD, and very often there are multiple overlapping causes. It is hard to improve cough in these patients, with available medicines providing limited relief. One explanation for this gap is an incomplete understanding of cough in ILD. To improve patients' cough there is a need to better understand its cause. In other lung diseases, such as asthma, doctors and scientists have used phlegm tests to measure inflammation in the lung, which helps them choose the right medicine for the right patient. This has not been done for ILD, even though it has recently been found that many patients with ILD and everyday cough have abnormal phlegm tests. Using this strategy in ILD could improve patients' cough and quality of life, and possibly even slow progression of the disease.

Detailed Description

SpECC-ILD is an open-label, randomized controlled trial assessing the efficacy of sputum-guided management (using sputum cytometry) compared to standard care over 16 weeks in patients with chronic cough and ILD.

A total of 80 participants will be enrolled and randomized in a 1:1 ratio to either sputum guided therapy or standard of care for a total of 16 weeks. Participants randomized to the intervention arm will receive open-label sputum-guided management of airway inflammation identified during screening. Participants in this arm will receive standard of care treatment as determined by their ILD specialist who will be blinded to the results of the sputum analysis.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
120
Inclusion Criteria
  • Written informed consent consistent with ICH-GCP and local laws, signed prior to any study procedures being performed
  • Age >18 years
  • A clinical diagnosis of ILD with accepted specific diagnoses including:
  • Idiopathic pulmonary fibrosis (IPF)
  • Chronic hypersensitivity pneumonitis associated ILD (CHP-ILD)
  • Connective tissue disease associated ILD (CTD-ILD)
  • Pneumoconiosis
  • Daily Cough for at least 8 weeks
  • Able to produce an adequate sample with sputum induction
Exclusion Criteria
  • Patients with a diagnosis of systemic sclerosis associated ILD (SSc-ILD) or sarcoidosis
  • Cause of cough attributed to a known etiology (ex. ACE-inhibitor, uncontrolled gastroesophageal reflux or upper airway cough syndrome, acute viral illness)
  • Current use of inhaled corticosteroids
  • Current use of systemic corticosteroids (prednisone equivalent > 20mg/day)
  • Current use of chronic antibiotics
  • Airflow obstruction (ie. pre-bronchodilator FEV1/FVC ratio < 0.7)
  • History of physician-diagnosed asthma
  • History of emphysema
  • A history of cholestatic jaundice or hepatic dysfunction associated with prior use of azithromycin
  • Moderate to severe hepatic dysfunction with a Child Pugh score >10
  • Known allergy or hypersensitivity to inhaled corticosteroids or macrolide antibiotics
  • Corrected QT-interval (QTc) on screening electrocardiogram (ECG) of > 450ms
  • An established history of untreated atypical mycobacterial infection
  • A history of hearing impairment, tinnitus, or vertigo
  • Medication use likely to suppress cough (ex: morphine, gabapentin, amitriptyline)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sputum-guided managementSputum-guided managementDuring Weeks 0 to 16, participants randomized to the intervention arm will receive open-label sputum-guided management of airway inflammation (Table 1 in protocol) identified during screening (Figure 2 in protocol). Airway eosinophilia will be treated with regular inhaled corticosteroids based on the severity of eosinophilic inflammation. In participants with airway neutrophilia, as per the standard of care, sputum culture and sensitivity will be sent, and pathogenic organisms treated. Those participants with airway neutrophilia with negative cultures will be treated with thrice weekly Azithromycin (250mg). Combined eosinophilia and neutrophilia will receive treatment with both ICS and Azithromycin as per Table 2 in protocol.
Standard of CareStandard of CareParticipants in this arm will receive standard of care treatment as determined by their ILD specialist who will be blinded to the results of the sputum analysis.
Primary Outcome Measures
NameTimeMethod
Change in hourly cough frequency16 weeks

The difference in hourly cough frequency over a 24-hour period between baseline and end of study.

Secondary Outcome Measures
NameTimeMethod
Change in FVC16 weeks

The difference in forced vital capacity (as obtained by spirometry) between baseline and end of study

Completion rates for Bi-weekly LCQ16 weeks

Rates of completion for bi-weekly LCQ

Change in Leicester Cough Questionnaire16 weeks

The difference in LCQ between baseline and end of study

Change in sputum eosinophils16 weeks

The difference in sputum eosinophil percent between baseline and end of study

Study medication adherence rate16 weeks

Rates of adherence to study medications

Change in FEV116 weeks

The difference in forced expiratory volume in 1 second (as obtained by spirometry) between baseline and end of study

Change in King's Brief ILD Questionnaire16 weeks

The difference in KB-ILD between baseline and end of study

Change in sputum total cell count16 weeks

The difference in sputum total cell count between baseline and end of study

Change in sputum neutrophils16 weeks

The difference in sputum neutrophil percent between baseline and end of study

Adverse events16 weeks

Adverse events reported by participants

Serious adverse events16 weeks

Serious adverse events reported by participants

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