Thermotherapy Against Persistent Bacterial LUNG Infections (THERM-A-LUNG)

The aim of this study is to determine whether an intervention with frequent thermotherapy will be able to reduce the amount of colonizing bacteria in the bronchoalveolar lavage sample and eradicate the colonizing bacteria.

Study Overview

• Status: Recruiting
• Conditions: Bronchiectasis; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease; Asthma; Copd; Chronic Lung Infections
• Intervention / Treatment: Other: Thermotherapy/sauna bath

Detailed Description

Normally, bacterial lung infections are acute such as community-acquired pneumonia and typically resolve after antibiotic therapy without leaving much lasting damage on the lungs. However, a great amount of persons with disrupted clearance of mucus and/or lung immune system get persistent lung infections, which can be life-long, usually do not resolve even with antibiotics, and can greatly increase morbidity and mortality. IThese persistent lung infections are thus characterized by stable periods with exacerbations inbetween, akin to chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. In addition, it has not been thoroughly investigated whether antibiotic regimens have an effect on disease control, as biofilm formation prevents antibiotics from killing the bacteria.

This is a randomized, controlled, multi-center, superiority trial evaluating the effect of a thermotherapy intervention, consisting of min. 7 minutes stay in min. 85℃ environment at least 4 times a week for 6 months, in persons with persistent bacterial lung infection, defined as min. 2 positive cultures during the last 24 months for one of the following bacteria: Pseudomonas aeruginosa, Achromobacter xylosoxidans, Stenotrophomonas maltophilia, Klebsiella oxytoca, Klebsiella pneumoniae, Haemophilus influenzae or Staphylococcus aureus, incl. 1 positive culture after attempted eradication therapy. The aim of the study is to investigate whether thermotherapy may offer a valid proposal for treatment of chronic lung infections.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamad I Saeed, MD; Phone Number: +4538673555; Email: mohamad.isam.saeed.02@regionh.dk

Study Locations

• Denmark
  • Region Hovedstaden
    • Hellerup, Region Hovedstaden, Denmark, 2900
      • Recruiting
      • Herlev and Gentofte University Hospital
      • Contact: Mohamad I Saeed, MD; Email: mohamad.isam.saeed.02@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Competent and capable
• FEV1>1,0 L
• Have had a positive culture from sputum or BAL min. 2 times in the last 24 months for bacteria of the species: Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Staphylococcus aureus, Haemophilus influenzae, Achromobacter xylosoxidans, Klebsiella oxytoca or Klebsiella pneumoniae. In addition, min. 1 positive culture after treatment with antibiotics
• Willing to go to a sauna (min. temperature of 85℃ for at least 7 minutes) four times weekly for six months or avoid going to a sauna for six months

Exclusion Criteria:

• Allergy to lidocaine and/or midazolam
• Contraindications to bronchoscopy
• Previous severe laryngospasm (intubation requiring)
• Pregnancy/breastfeeding
• Severe linguistic problems or inability to give informed consent
• Severe mental illness that is not controlled with medication. NB: Patients with controlled mental illness can be included and will be asked on an equal footing as others

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thermotherapy/sauna bath; Must go to a sauna (min. Temperature 85℃) min. 4 times a week for 6 months. Each sauna bath must last at least 7 minutes. The intervention patients receive a subscription card for a sauna during the period. Patients will still receive pre-existing treatment	Other: Thermotherapy/sauna bath; Thermotherapy/sauna bath
No Intervention: No thermotherapy/sauna bath; Not allowed to go to a sauna for 6 months. Patients who come to do so, by e.g. an oversight, however, remain in the study, to avoid introducing bias. It will be registered as a "protocol violation", but the patient will be included in Intention To Treat analysis and modified Intention To Treat analysis. Patients will still receive pre-existing treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in bacterial growth (measured in cfu/mL) from bronchoalveolar lavage after 6 months	6 months
Eradication of the cultured bacteria at baseline, defined by no use of antibiotics the last 14 days at the follow-up assessment after 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of hospitalizations for all causes or death within 6 months	6 months
Number of antibiotic treatment regimes within 6 months	6 months
Physical performance measured by distance walked over 6 minutes	6 months
Changes in FEV1 after 6 months	6 months
Changes in BMI after 6 months	6 months
Clinically relevant changes in Chronic Obstructive Pulmonary Disease Assessment Test-score (range from 0-40, higher is worse) after 6 months	6 months
Changes in status from Medical Research Council-dyspnea score (range from 0-5, higher is worse) from <3 to 3≥, after 6 months	6 months
Changes in composition of the lung microbiota after 6 months	6 months
Changes in abundance of the lung microbiota after 6 months	6 months

Collaborators and Investigators

• Sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: April 22, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Bronchial Diseases; Chronic Disease; Bronchiectasis; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Infections; Communicable Diseases
• Other Study ID Numbers: THERM-A-LUNG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No