Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that pose an increasing threat to public health. Over the past 2 decades, the burden of disease attributable to these organisms has increased with the incidence surpassing that of tuberculosis in many areas. Mycobacterium avium complex (MAC) accounts for over 75% of the pulmonary infections due to NTM. Unfortunately, pulmonary MAC treatment is difficult because of cost, lack of clearly defined, patient-oriented outcome measures, and poorly tolerated medications. Current recommendations for treatment of pulmonary MAC disease are based on small single site, uncontrolled, non-comparative studies, usually of severe or recalcitrant disease. We propose a 1-year planning grant in order to achieve 2 primary aims: 1) To create the NTM Research Consortium (NTMRC) and 2) To design a Phase II open clinical trial that will assess the safety, tolerability, and efficacy of a standard 3-drug treatment regimen for previously untreated patients with pulmonary MAC infection. Our secondary aims are to: 1) establish an organizational and committee structure for the NTMRC; 2) develop and test case report forms for the planned trial; 3) develop and submit protocols for review by the site institutional review boards; 4) develop manuals of operations for the clinical trial and laboratory methodology; and 5) establish a contractual relationship with a data management and biostatistical vendor. The NTMRC will include clinical sites that care for many patients with NTM infections and highly recognized reference laboratories experienced in pharmacokinetics as well as NTM microbiology. Investigators from clinical and laboratory sites will collaborate to design the clinical trial and all study-related materials. National Jewish Medical and Research Center (NJC) will be the coordinating center. Clinical sites will be the University of Texas Health Center Tyler (UTHCT), Duke University, and the Laboratory of Clinical Infectious Diseases at the National Institute of Allergy and Infectious Diseases. The Infectious Disease Pharmacokinetics and Mycobacterial Reference Laboratories at NJC and the Mycobacterial Reference Laboratories at UTHCT will provide critical laboratory support for the clinical trial. The NTMRC will develop working groups to facilitate design of the study and development of study materials. Communication will be fostered through frequent teleconferences, 2 meetings, and a study website. Substudies will be developed during the planning process and attached to the parent trial. By the end of the planning period, we will have a finalized protocol and necessary study materials available to begin enrollment.

R34AI072271

2006-09-01

2008-08-31