Tuberculosis, Pulmonary Clinical Trial
— PMTforDR-TBOfficial title:
Multi Center Clinical Research and Evaluation of Melting Technology for Rapid Detection of Drug Resistant Tuberculosis
Background:
Drug resistant tuberculosis is a serious public health problem that threatens the health of
human life and the development of society and economy. At present, the diagnosis of
drug-resistant tuberculosis mainly depends on traditional drug susceptibility test. But it
is limited in Mycobacterium tuberculosis slow growth speed, traditional solid drug
sensitivity test usually need to 3 months to results, delay the development of drug
resistance in patients with effective treatment. Probe melting curves resistance detection
technology is the recent emergence of a new molecular biology and drug resistant
tuberculosis detection technology, probe melting curves with different fluorescent labeled
probe coverage detection specific to M.tuberculosis drug resistance determining region,
through changes in the melting point of the probe hybridization, acquire mutation
information of detection region, shorten detection time and detect nonuniform resistance.
In this study, by selecting a nationally representative in different levels of hospitals
jointly launched multi center, large sample clinical assessment, completed the comprehensive
evaluation of sensitivity, specificity and health economics of drug resistant pulmonary
tuberculosis, especially resistance to multidrug and extensively drug-resistant TB patients
detection,in order to evaluate the rapid, accurate and economic and appropriate technology
of drug resistance pulmonary tuberculosis detection.
In order to accomplish the overall goal of the project, in the framework of the overall
design, according to the principles of the core tasks are divided into four sub topics,
namely:
Sub topic 1 of the core mission is included in 3100 cases of smear positive pulmonary TB
suspicious symptoms, from which selected more than 1000 cases of drug-resistant pulmonary
tuberculosis patients, using MGIT liquid culture and drug sensitivity test as the gold
standard,evaluate the sensitivity and specificity of probe melting curves in detction of
resistance of four kinds of anti tuberculosis drug to Mycobacterium tuberculosis; Sub topic
2 core task is including at least 500 cases of culture positive pulmonary tuberculosis
patients and treatment follow-up, using MGIT liquid culture and drug sensitivity test as the
gold standard, evaluate the application value of probe melting curves for monitoring
spectrum changes of drug resistance of Mycobacterium tuberculosis during pulmonary
tuberculosis treatment.
The core mission of sub topic 3 is to project implementation of hospital as the research
site,acquire the cost-effect evaluation and analysis by comparing probe melting technology
with Mycobacterium tuberculosis MGIT liquid culture, and drug sensitivity test with xpert
MTB/RIF technology.
Status | Not yet recruiting |
Enrollment | 3100 |
Est. completion date | June 2019 |
Est. primary completion date | December 2018 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. During the study of all smear positive pulmonary tuberculosis with suspicious symptoms 2. Can provide 3-4ml sputum samples three times in 2 days 3. Informed consent Exclusion Criteria: - The quality of the sputum sample is not qualified (the sputum sample is less than 3ml or saliva sputum) |
Observational Model: Case-Only, Time Perspective: Prospective
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Beijing Hospital |
Banada PP, Sivasubramani SK, Blakemore R, Boehme C, Perkins MD, Fennelly K, Alland D. Containment of bioaerosol infection risk by the Xpert MTB/RIF assay and its applicability to point-of-care settings. J Clin Microbiol. 2010 Oct;48(10):3551-7. doi: 10.11 — View Citation
Blakemore R, Story E, Helb D, Kop J, Banada P, Owens MR, Chakravorty S, Jones M, Alland D. Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol. 2010 Jul;48(7):2495-501. doi: 10.1128/JCM.00128-10. Epub 2010 May 26. — View Citation
Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A, Jones M, O'Brien SM, Persing DH, Ruesch-Gerdes S, Gotuzzo E, Rodrigues C, Alland D, Perkins MD. Rapid molecular detection of tuberculos — View Citation
Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, Lijmer JG, Moher D, Rennie D, de Vet HC; Standards for Reporting of Diagnostic Accuracy. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. — View Citation
El-Hajj HH, Marras SA, Tyagi S, Kramer FR, Alland D. Detection of rifampin resistance in Mycobacterium tuberculosis in a single tube with molecular beacons. J Clin Microbiol. 2001 Nov;39(11):4131-7. — View Citation
Farmer P, Bayona J, Becerra M, Furin J, Henry C, Hiatt H, Kim JY, Mitnick C, Nardell E, Shin S. The dilemma of MDR-TB in the global era. Int J Tuberc Lung Dis. 1998 Nov;2(11):869-76. — View Citation
Getahun H, Harrington M, O'Brien R, Nunn P. Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet. 2007 Jun 16;369(9578):2042-9. Review. — View Citation
Havlir DV, Getahun H, Sanne I, Nunn P. Opportunities and challenges for HIV care in overlapping HIV and TB epidemics. JAMA. 2008 Jul 23;300(4):423-30. doi: 10.1001/jama.300.4.423. — View Citation
Helb D, Jones M, Story E, Boehme C, Wallace E, Ho K, Kop J, Owens MR, Rodgers R, Banada P, Safi H, Blakemore R, Lan NT, Jones-López EC, Levi M, Burday M, Ayakaka I, Mugerwa RD, McMillan B, Winn-Deen E, Christel L, Dailey P, Perkins MD, Persing DH, Alland — View Citation
Hillemann D, Rüsch-Gerdes S, Richter E. Application of the Capilia TB assay for culture confirmation of Mycobacterium tuberculosis complex isolates. Int J Tuberc Lung Dis. 2005 Dec;9(12):1409-11. — View Citation
Palomino JC. Molecular detection, identification and drug resistance detection in Mycobacterium tuberculosis. FEMS Immunol Med Microbiol. 2009 Jul;56(2):103-11. doi: 10.1111/j.1574-695X.2009.00555.x. Epub 2009 Mar 18. Review. — View Citation
Perkins MD, Cunningham J. Facing the crisis: improving the diagnosis of tuberculosis in the HIV era. J Infect Dis. 2007 Aug 15;196 Suppl 1:S15-27. Review. — View Citation
Piatek AS, Tyagi S, Pol AC, Telenti A, Miller LP, Kramer FR, Alland D. Molecular beacon sequence analysis for detecting drug resistance in Mycobacterium tuberculosis. Nat Biotechnol. 1998 Apr;16(4):359-63. — View Citation
Policy Statement: Automated Real-Time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF System. Geneva: World Health Organization; 2011. — View Citation
Raja S, Ching J, Xi L, Hughes SJ, Chang R, Wong W, McMillan W, Gooding WE, McCarty KS Jr, Chestney M, Luketich JD, Godfrey TE. Technology for automated, rapid, and quantitative PCR or reverse transcription-PCR clinical testing. Clin Chem. 2005 May;51(5):8 — View Citation
Sanchez-Padilla E, Dlamini T, Ascorra A, Rüsch-Gerdes S, Tefera ZD, Calain P, de la Tour R, Jochims F, Richter E, Bonnet M. High prevalence of multidrug-resistant tuberculosis, Swaziland, 2009-2010. Emerg Infect Dis. 2012 Jan;18(1):29-37. doi: 10.3201/eid — View Citation
Sanchez-Padilla E, Merker M, Beckert P, Jochims F, Dlamini T, Kahn P, Bonnet M, Niemann S. Detection of drug-resistant tuberculosis by Xpert MTB/RIF in Swaziland. N Engl J Med. 2015 Mar 19;372(12):1181-2. doi: 10.1056/NEJMc1413930. — View Citation
Siu GK, Zhang Y, Lau TC, Lau RW, Ho PL, Yew WW, Tsui SK, Cheng VC, Yuen KY, Yam WC. Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis. J Antimicrob Chemother. 2011 Apr;66(4): — View Citation
Urbanczik R, Rieder HL. Scaling up tuberculosis culture services: a precautionary note. Int J Tuberc Lung Dis. 2009 Jul;13(7):799-800. — View Citation
Urdea M, Penny LA, Olmsted SS, Giovanni MY, Kaspar P, Shepherd A, Wilson P, Dahl CA, Buchsbaum S, Moeller G, Hay Burgess DC. Requirements for high impact diagnostics in the developing world. Nature. 2006 Nov 23;444 Suppl 1:73-9. — View Citation
Uys PW, Warren RM, van Helden PD. A threshold value for the time delay to TB diagnosis. PLoS One. 2007 Aug 22;2(8):e757. — View Citation
Van Rie A, Enarson D. XDR tuberculosis: an indicator of public-health negligence. Lancet. 2006 Nov 4;368(9547):1554-6. — View Citation
Yagui M, Perales MT, Asencios L, Vergara L, Suarez C, Yale G, Salazar C, Saavedra M, Shin S, Ferrousier O, Cegielski P. Timely diagnosis of MDR-TB under program conditions: is rapid drug susceptibility testing sufficient? Int J Tuberc Lung Dis. 2006 Aug;1 — View Citation
* Note: There are 23 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | the sensitivity and specificity of probe melting curves technology | assess the sensitivity and specificity of probe melting curves for four kinds of anti tuberculosis drug resistance to Mycobacterium tuberculosis. | up to 3.5 years | No |
Primary | Comparison of diagnostic efficacy | Using Xpert-MTB/RIF as control technology, the diagnostic efficacy of two kinds of drug resistance detection technology was compared. | from January,2015 to December,2018 | No |
Primary | Evaluation of the application value of probe melting curve technology | For the first time in China to carry out drug-resistant TB rapid detection technology appllied in the follow-up, improve the resistance detection technology to monitor the change of TB drug resistance spectrum in the treatment of pulmonary tuberculosis.Selecting patients with MGIT liquid culture positive pulmonary tuberculosis(selected from sub topic1) were included in the study,at least 500 patients were included in the study.Observe the outcomes and the change of drug resistance spectrum.drug-resistant TB rapid detection technology applied in the follow-up of patients with pulmonary TB by monitoring TB drug resistance spectrum change,provides the basis for the resistant phenotype and genotype identification and diagnosis of nonuniform resistance.Data statistics and analysis:95% confidence intervals, chi square test and Kappa test were calculated respectively. | up to 3.5 years | No |
Primary | analyze the cost-effect assessment of probe melting curve technology and other two kinds of detection methods | Complete the cost-effectiveness assessment analysis of the probe melting curve technology compared with Mycobacterium tuberculosis MGIT liquid culture and drug sensitivity test,and xpert MTB / RIF technology. Methods:Using cost analysis and acceptability questionnaire.Each of the implementation of the hospital, collecting the basic data and input the costs into the software,using opportunity cost method. |
up to 3.5 years | No |
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