Prospective Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria

Cystic Fibrosis Clinical Trial

— pHALT NTM  

Official title:

Prospective Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria Among People With Cystic Fibrosis

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05686837
• Other study ID #: HS-3175-528
• Status: Enrolling by invitation
• Start date: December 28, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2023
• Source: National Jewish Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Pulmonary NTM infection is recognized as one of the most challenging infections to treat among people with cystic fibrosis (PwCF), notable for prolonged treatment courses and often poor response to therapy. Positive cultures for NTM occur in about 20% of children and adults with cystic fibrosis (CF). However, the source of NTM infection, modes of transmission, and exposure risks are poorly understood. It is thought that NTM is primarily acquired from environmental sites including soil and water as well as water supply systems to homes, hospitals, and clinics and from aerosols generated by flowing water from taps, showers, and fountains. Nonetheless, no direct molecular link has been established between environmental NTM and respiratory CF NTM. Healthcare-associated transmission of NTM among CF patients has been suspected and is of growing concern for CF Centers worldwide. Widespread global transmission of NTM, potentially via person-to-person transmission of fomites and aerosols has been reported. The parent HALT NTM study developed and published a standardized epidemiologic outbreak toolkit for investigation of healthcare-associated NTM outbreaks in CF Care Centers. We are now moving to a prospective investigation, with the long-term goal of real-time early identification and mitigation of potential NTM outbreak investigations coupled with healthcare environmental sampling and home of residence watershed analysis of PwCF identified as belonging to an NTM cluster and receiving care at a single CF Care Center.

Description:

This is a prospective, multicenter, nonrandomized study to investigate potential NTM outbreaks in the six CF Care Centers currently enrolled in the HALT NTM study. The study will investigate potential episodes of healthcare-associated NTM transmission and/or acquisition within participating U.S. Care Centers, coupled with healthcare environmental sampling and home of residence watershed analysis.

PART A / Epidemiologic Investigation:

The Colorado NTM Outcome Measure Advancement Core National Resource Centers (CO-NRC) provides a national reference laboratory for CF NTM. NTM respiratory isolates received from CF Care Centers around the U.S. undergo culture, molecular identification, antimicrobial susceptibility, and whole genome sequencing (WGS). Using this approach, the CO-NRC has identified clusters of NTM isolates, defined as highly similar strains at the genomic level, harbored by two or more people with CF (pwCF) who are cared for at the same CF Care Center. These identifications have heightened our concern for potential healthcare-associated NTM acquisition originating from patient-to- patient transmission or a common environmental source within Centers.

Using integrated clinical and epidemiological research methods, the parent HALT NTM study developed and validated a healthcare-associated epidemiologic investigation toolkit that can identify overlaps in source(s) of care between patients with highly similar NTM isolates in a Center. The parent HALT NTM toolkit facilitates a stepwise process by which individual Centers perform epidemiologic evaluation of patients identified by the CO-NRC as being infected with clustered NTM isolates.

The retrospective parent HALT NTM study of potential NTM outbreaks has been completed at six participating CF Care Centers. In the pHALT NTM study, participating sites will prospectively submit all respiratory NTM isolates from all PwCF receiving routine care over a two-year period to NJH Advanced Diagnostic Laboratories. All NTM isolates will be stored in the Biobank within the NTM Culture, Biorepository and Coordinating Core (Project ID: HS3149) and used for research purposes. The CO-NRC will utilize an honest broker to de-identify NTM isolates and will culture, bank, and extract DNA. The CO-NRC de-identified isolates will then be analyzed as previously described.

When highly related clusters are identified, the HALT NTM epidemiologic investigation toolkit will be independently used by each participating Center to identify overlaps in source(s) of care between patients with highly similar NTM isolates. Additionally, PwCF identified as being infected with highly similar NTM isolates will be asked to complete an online survey. The survey will ask the subject's basic demographic information, query their interactions with other PwCF, and document where they receive CF care.

PART B / Dust and Water Biofilm Collection:

Clustered NTM isolates could originate from a shared healthcare water source. Biofilms from healthcare dust and water supplies will be collected and NTM recovered, identified, and sequenced to determine if the respiratory CF NTM strain genotype is similar to those recovered from the healthcare dust and water supply.

Part C/Home of Residence Watershed Mapping: Clustered NTM isolates could originate from a shared home of residence water supply. PwCF having clustered NTM isolates will be asked to complete an online survey. The survey will ask subjects for their current and last 2 year's home address. The home of residence for PwCF identified in clusters will be extracted and geocoded to latitude and longitude coordinates and mapped to Hydrologic Unit Code level watersheds to determine if clustered PwCF share a common home of residence water supply source.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 99 Years

Eligibility

Inclusion Criteria:

• Diagnosis of CF consistent with the 2017 CFF guidelines.

• Male or female participant of any age who has a history of NTM or a first positive NTM culture collected as part of routine clinical care from expectorated sputum, induced sputum and/or bronchoalveolar lavage.

Exclusion Criteria:

• No diagnosis of CF

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Mycobacterium Infections
• Nontuberculous Mycobacterial Pulmonary Infection

Locations

Country	Name	City	State
United States	National Jewish Health	Denver	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
National Jewish Health	Cystic Fibrosis Foundation

Country where clinical trial is conducted

United States, 

References & Publications (2)

Gross JE, Caceres S, Poch K, Hasan NA, Davidson RM, Epperson LE, Lipner E, Vang C, Honda JR, Strand M, Strong M, Saiman L, Prevots DR, Olivier KN, Nick JA. Healthcare-associated links in transmission of nontuberculous mycobacteria among people with cystic fibrosis (HALT NTM) study: Rationale and study design. PLoS One. 2021 Dec 20;16(12):e0261628. doi: 10.1371/journal.pone.0261628. eCollection 2021. — View Citation

Gross JE, Caceres S, Poch K, Hasan NA, Jia F, Epperson LE, Lipner E, Vang C, Honda JR, Strand M, Calado Nogueira de Moura V, Daley CL, Strong M, Davidson RM, Nick JA. Investigating Nontuberculous Mycobacteria Transmission at the Colorado Adult Cystic Fibrosis Program. Am J Respir Crit Care Med. 2022 May 1;205(9):1064-1074. doi: 10.1164/rccm.202108-1911OC. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epidemiologic Investigation	Identification of a shared healthcare-associated source(s) between patients in a CF Care Center.	3 years
Primary	Dust and Water Biofilm Collection	Identification of healthcare dust and water biofilm NTM isolates that are highly related to the isolates recovered from PwCF.	3 years
Primary	Home of Residence Watershed Mapping	The primary endpoint is identification of common watersheds among pwCF infected with clustered NTM isolate.	3 years
Secondary	Epidemiologic Investigation	Incidence and prevalence of CF NTM species/subspecies by geographical region. Between Center comparisons of genetic similarity and patterns of potential transmission.; Banking of isolates for ex vivo analysis.	3 years
Secondary	Dust and Water Biofilm Collection	Incidence and prevalence of healthcare-associated dust and water biofilm NTM species/subspecies by geographical region.	3 years