Deadline: Jul 27, 2014 23:59 U.S. Eastern Daylight Time (EDT)
CRDF Global is currently accepting proposals from clinical and laboratory research teams to perform a novel methodological variation on an “Early Bactericidal Activity” (EBA) study to establish data on the utility of key anti-TB drugs in specific situations. This research is based on the premise that optimal treatment of drug-resistant tuberculosis is based on timely, accurate in-vitro drug susceptibility test (DST) results. Standard DSTs, however, may generate ambiguous results in at least three different situations: (1) when two closely related drugs from the same chemical class of antibiotics differ in their in vitro effect on a patient’s isolate of M. tuberculosis. (2) if higher concentrations of a drug are bactericidal even though standard concentrations are not. (3) when DNA testing demonstrates a mutation(s) in a drug resistance-associated gene, while phenotypic DST results indicate susceptibility to the given drug. The goal of this research study is to generate controlled, reliable, clinically relevant evidence from study enrollants to inform treatment decisions in these situations.
Sub-recipient funding for this program is provided by CRDF Global through a Cooperative Agreement from the U.S. Centers for Disease Control and Prevention (CDC), a major operating unit of the U.S. Department of Health and Human Services (DHHS). For additional information on the U.S. CDC, please visit their website at: www.cdc.gov.
The specific objectives of the research study are to determine, in patients with drug-resistant tuberculosis:
- The bactericidal activity of rifabutin in patients whose baseline DST results demonstrate susceptibility to rifabutin and resistance to rifampicin
- The bactericidal activity of high-dose isoniazid (5 mcg/ml in agar, 2 mcg/ml in broth) in patients whose baseline DST results demonstrate susceptibility to high concentrations of isoniazid and resistance to low concentrations of isoniazid
- The bactericidal activity of rifampicin when an approved molecular assay demonstrates genetic mutations associated with rifampicin resistance, but the phenotypic testing demonstrates susceptibility to rifampicin
- The bactericidal activity of moxifloxacin in patients whose baseline DST results demonstrate susceptibility to moxifloxacin and resistance to ofloxacin
- The bactericidal activity of amikacin and capreomycin in patients whose baseline DST results demonstrate susceptibility to either of these two drugs and resistance to kanamycin
In order to be eligible to receive funding under this program, applications must meet ALL of the following criteria:
- Must have or partner with a Biosafety Level 3 laboratory that has demonstrated capacity to perform advanced, non-routine microbiological procedures including quantitative cultures on solid media such as Middlebrook agar, cultures and DST in BACTEC™ MGIT 960, and either GeneXpert® or Hain GenoType® MTBDRplus assays. If the site’s laboratory does not have this capacity in place at the time of this application, the site must be able to implement and validate these procedures, through proficiency testing within 3 months of the award. In this case, the applicant must make the case convincingly that the laboratory can implement, validate, and perform the required procedures in a timely and accurate manner
- Must have documented sufficient numbers of patients with both drug resistant TB and positive sputum microscopy for acid fast bacilli (AFB), that is, at least 50 patients per year with rifampicin-resistant TB and 100 patients per year with isoniazid-resistant TB
- Must have the ability to hospitalize patients with appropriate biosafety precautions
- Must be able to administer treatment via direct observation by a health care professional (e.g. doctor, nurse, community health worker) who has been trained to detect adverse events to MDR-TB treatment
- Proposals must include at least one Principal Investigator (PI) 1) possessing the degree of Ph.D., M.D., or the equivalent research experience, and 2) having at least five scientific publications in peer-reviewed scientific literature. The PI will have overall responsibility for the project, coordinating all project participants and institutions. Proposals will be accepted from teams based in two or more countries, but each team will need a designated co-PI who will share the responsibility for the project with his/her counterparts from each institute
- PIs must have documented previous experience with clinical trials
- All team members must have clearly defined roles described in the narrative with the appropriate knowledge, skills, and experience (included in Form B and their individual CVs)
If the applicant has received his or her academic degree in the past six (6) years, three (3) publications are required.
For more information, read the full Request for Proposals (RFP): BBA_RFP_July2014