The Evaluation of a Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB (STREAM)

This study is currently recruiting participants.

See

Contacts and Locations

Verified July 2017 by IUATLD, Inc

Sponsor:

Collaborator:

Medical Research Council

Information provided by (Responsible Party):

IUATLD, Inc

ClinicalTrials.gov Identifier:

NCT02409290

First received: March 31, 2015

Last updated: July 3, 2017

Last verified: July 2017

History of Changes

Purpose

Tuberculosis (TB) is a common, infectious, bacterial disease that is spread when an infected person transmits their saliva through the air by coughing or sneezing. Despite the availability and effectiveness of affordable six-month treatments for tuberculosis (TB), the worldwide control of this disease is currently being impacted by the emergence of multidrug resistant TB (MDR-TB).

MDR-TB refers to TB that is resistant to at least isoniazid and rifampicin. These are the two most powerful first-line drugs used to treat pulmonary TB. MDR-TB usually develops while a person is taking TB treatment due to either inappropriate treatment or failure of patients to comply with their treatment. This strain of drug-resistant bacteria can also be spread to other people through the air.

MDR-TB leads to a considerable reduction in the effectiveness of standard short-length treatments and currently the standard treatments for MDR-TB can last as long as 24 months. With the incident rate of MDR-TB on the rise (511,000 new cases in 2007) and the lengthy duration of current treatments there is a need to investigate whether a shorter-length treatment using effective drugs is a global possibility.

Three short course regimens of drugs will be evaluated alongside the World Health Organisation recommended 24 month regimen for the treatment of MDR-TB.

A total of at least 1155 participants with MDR-TB will be recruited and followed for a total of 132 weeks.

Condition	Intervention	Phase
MDR-TB	Drug: Regimen A locally-used WHO-approved MDR-TB regimen Drug: Moxifloxacin Drug: Clofazimine Drug: Ethambutol Drug: Pyrazinamide Drug: Isoniazid Drug: Prothionamide Drug: Kanamycin Drug: Levofloxacin Drug: Bedaquiline	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	STREAM: The Evaluation of a Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Genetic and Rare Diseases Information Center resources: Tuberculosis

U.S. FDA Resources

Further study details as provided by IUATLD, Inc:

Primary Outcome Measures:

STREAM Stage 2 Primary Outcome Measure (the proportion of patients with a favourable outcome at Week 76) [ Time Frame: 76 weeks ]
The primary efficacy outcome of the STREAM Stage 2 comparison is status at Week 76 i.e. the proportion of patients with a favourable outcome at Week 76


Estimated Enrollment:	1155
Study Start Date:	April 2016
Estimated Study Completion Date:	December 2021
Estimated Primary Completion Date:	April 2021 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Regimen A Regimen A locally-used WHO-approved MDR-TB regimen Regimen A, is the locally-used WHO-approved MDR-TB regimen in a country or site. It will be used in the secondary analysis of the study only.	Drug: Regimen A locally-used WHO-approved MDR-TB regimen Drug: Locally-used WHO-approved MDR-TB regimen
Active Comparator: Regimen B Product and dose for [<33 kg, 33-50kg, >50 kg] respectively: Moxifloxacin [400mg, 600mg, 800mg]; Clofazimine [50mg,100mg,100mg]; Ethambutol [800mg,800mg,1200mg]; Pyrazinamide [1000mg,1500mg, 2000mg]; Isoniazid 300mg, 400mg, 600mg]; Prothionamide [250mg,500mg,750mg]; Kanamycin [15mg per kilogram body weight (maximum 1g)].	Drug: Moxifloxacin Moxifloxacin is an 8-methoxy quinolone, and an anti-bacterial fluoroquinolone Other Name: Avelox Drug: Clofazimine Clofazimine, is an antileprosy and anti-bacterial agent. Its chemical name is 3-(p-chloroanilino)-10-(p-chlorophenyl)-2, 10-dihydro-2-sopropyliminophenazine. Other Name: Lamprene Drug: Ethambutol Ethambutol is a bacteriostatic that acts against virtually all strains of Mycobacterium tuberculosis and M. bovis and is also active against other mycobacteria such as M. Kansasii. Other Name: Myambutol Drug: Pyrazinamide Pyrazinamide is bactericidal against intracellular mycobacterium tuberculosis. It is a prodrug that is converted into its active form, pyrazinoic acid, by a mycobacterial enzyme, pyrazinamidase, as well as through hepatic metabolism. Other Name: Zinamide Drug: Isoniazid Isoniazid is a bactericidal in vitro and in vivo against actively dividing tubercle bacilli. Its primary action is to inhibit the synthesis of long-chain mycolic acids, which are unique constituents of mycobacterial cell wall. Other Names: Nydrazid Isotamine Drug: Prothionamide Prothionamide has a bacteriostatic action. Other Name: Peteha Drug: Kanamycin Kanamycin is a bactericidal antibiotic from the group of aminoglycosides. Other Name: Kantrex
Experimental: Regimen C Product and dose for [<33kg, 33-50kg, >50 kg] respectively: Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin [750mg, 750mg,1000mg]; Clofazimine [50mg, 100mg, 100mg]; Ethambutol [800mg, 800mg, 1200mg]; Pyrazinamide [1000mg,1500mg, 2000mg]; Isoniazid [300mg, 400mg, 600mg]; Prothionamide [250mg, 500mg,750mg].	Drug: Clofazimine Clofazimine, is an antileprosy and anti-bacterial agent. Its chemical name is 3-(p-chloroanilino)-10-(p-chlorophenyl)-2, 10-dihydro-2-sopropyliminophenazine. Other Name: Lamprene Drug: Ethambutol Ethambutol is a bacteriostatic that acts against virtually all strains of Mycobacterium tuberculosis and M. bovis and is also active against other mycobacteria such as M. Kansasii. Other Name: Myambutol Drug: Pyrazinamide Pyrazinamide is bactericidal against intracellular mycobacterium tuberculosis. It is a prodrug that is converted into its active form, pyrazinoic acid, by a mycobacterial enzyme, pyrazinamidase, as well as through hepatic metabolism. Other Name: Zinamide Drug: Isoniazid Isoniazid is a bactericidal in vitro and in vivo against actively dividing tubercle bacilli. Its primary action is to inhibit the synthesis of long-chain mycolic acids, which are unique constituents of mycobacterial cell wall. Other Names: Nydrazid Isotamine Drug: Prothionamide Prothionamide has a bacteriostatic action. Other Name: Peteha Drug: Levofloxacin Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class that acts on the DNA-DNA-gyrase complex and topoisomerase IV. It is the S (-) enantiomer of the racemic active substance ofloxacin. Other Name: Levaquin Drug: Bedaquiline Bedaquiline is a novel diarylquinoline antibiotic with bactericidal activity Other Name: SIRTURO
Experimental: Regimen D Product and dose for [<33kg, 33 to<40kg, 40-50kg, >50-60 kg, >60 kg] respectively: Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin [750mg, 750mg, 750mg, 1000mg, 1000mg]; Clofazimine [50mg, 100mg, 100mg, 100mg, 100mg]; Pyrazinamide [1000mg,1500mg, 1500mg, 2000mg, 2000mg]; Isoniazid [400mg, 500mg, 600mg, 800mg, 900mg]; Kanamycin [15 mg per kilogram body weight (maximum 1g)].	Drug: Clofazimine Clofazimine, is an antileprosy and anti-bacterial agent. Its chemical name is 3-(p-chloroanilino)-10-(p-chlorophenyl)-2, 10-dihydro-2-sopropyliminophenazine. Other Name: Lamprene Drug: Pyrazinamide Pyrazinamide is bactericidal against intracellular mycobacterium tuberculosis. It is a prodrug that is converted into its active form, pyrazinoic acid, by a mycobacterial enzyme, pyrazinamidase, as well as through hepatic metabolism. Other Name: Zinamide Drug: Isoniazid Isoniazid is a bactericidal in vitro and in vivo against actively dividing tubercle bacilli. Its primary action is to inhibit the synthesis of long-chain mycolic acids, which are unique constituents of mycobacterial cell wall. Other Names: Nydrazid Isotamine Drug: Kanamycin Kanamycin is a bactericidal antibiotic from the group of aminoglycosides. Other Name: Kantrex Drug: Levofloxacin Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class that acts on the DNA-DNA-gyrase complex and topoisomerase IV. It is the S (-) enantiomer of the racemic active substance ofloxacin. Other Name: Levaquin Drug: Bedaquiline Bedaquiline is a novel diarylquinoline antibiotic with bactericidal activity Other Name: SIRTURO

Hide Detailed Description

Detailed Description:

The STREAM study is an international, multi-centre, parallel-group, open-label, randomised, controlled trial in patients with multi-drug resistant tuberculosis (MDR-TB) including patients with rifampicin-resistant and isoniazid-sensitive TB.

Background and Rationale:

The current recommended treatment approach for MDR-TB is based largely on expert opinion and there is a lack of good evidence on optimal management. The World Health Organisation (WHO) guidelines for the treatment for MDR-TB recommends an intensive phase of treatment based on at least four drugs known to be effective and given for a minimum of 20 months. However, evaluation of the treatment success of such regimens in 9 countries varied from 25% to 73%. Van Deun et al (2010) reported excellent long-term outcomes in a cohort of over 200 patients in Bangladesh with MDR-TB who were treated with a regimen given for only nine months.

Bedaquiline is a novel diarylquinoline antibiotic with bactericidal activity. In a phase II trial of patients with MDR-TB time to culture conversion was significantly less in patients receiving bedaquiline compared to those receiving an optimised background regimen only (Diacon et al (2012). In December 2012 the US Food and Drug Administration (FDA) approved bedaquiline as part of the treatment regimen for MDR-TB when other agents are unavailable.

Study treatments

The treatments that are evaluated within the STREAM trial stage 2 are:

Regimen A The locally-used World Health Organization (WHO) approved MDR-TB regimen.

Regimen B Regimen B is based on the regimen described by Van Deun et al (2010) which reported excellent long-term outcomes in a cohort of over 200 patients in Bangladesh with MDR-TB who were treated with a regimen given for only nine months. In STREAM regimen B consists of clofazimine, ethambutol, moxifloxacin, and pyrazinamide given for 40 weeks, supplemented by isoniazid, kanamycin, and prothionamide in the first 16 weeks (intensive phase).

Regimen C Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).

Regimen D Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).

The primary objectives of the STREAM2 trial are:

To assess whether the proportion of patients with a favourable efficacy outcome on Regimen C, the fully oral regimen, is superior to that on Regimen B, the control regimen for Stage 2 at Week 76
To assess whether the proportion of patients with a favourable efficacy outcome on Regimen C, the fully oral regimen, is not inferior to that on Regimen B at Week 76, using a 10% margin of non-inferiority
To assess whether the proportion of patients with a favourable efficacy outcome on Regimen D, the shortened regimen, is not inferior to that on Regimen B at Week 76, using a 10% margin of non-inferiority.

The first primary objective, to assess the superiority of Regimen C over Regimen B, is a requirement of the US FDA; the second and third primary objectives are of programmatic relevance.

Study Population A total of at least 1155 participants with multi-drug resistance tuberculosis (MDR-TB) including patients with rifampicin-resistant and isoniazid-sensitive TB, will be recruited from sites in a number of countries. They will be randomised to either Regimen A, Regimen B, Regimen C, or Regimen D in a ratio 1:2:2:2 (i.e. 165 allocated to Regimen A, 330 allocated to Regimen B, 330 allocated to Regimen C, and 330 allocated to Regimen D).

All patients will be followed up to Week 132. The primary analysis will be based on the data accrued to Week 76 and is based on the proportion of patients with a favourable outcome at that time point ; the data accrued to Week 132 will be used in secondary analyses.

Although the STREAM study is an open-label study, wherever possible it will be conducted masked to treatment allocation.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Is willing and able to give informed consent to participate in the trial treatment and follow-up
Is aged ≥ 18 years
Has a positive Acid Fast Bacilli (AFB) sputum smear result at screening (at least scanty), unless they are HIV positive in which case a positive GeneXpert result within 4 weeks prior to screening is sufficient
Has evidence of resistance to rifampicin either by line probe assay (Hain Genotype21), GeneXpert or culture-based drug susceptibility testing (DST), from a test performed at screening or from a test performed within the 4 weeks prior to screening
Is willing to have an HIV test and, if positive, is willing to be treated with ART in accordance with the national policies but excluding ART contraindicated for use with bedaquiline
Is willing to use effective contraception: pre-menopausal women or women whose last menstrual period was within the preceding year, who have not been sterilised must use 2 methods of contraception; men who have not had a vasectomy must agree to use condoms.
Resides in the area and expected to remain for the duration of the study.
Has had a chest X-ray at that is compatible with a diagnosis of pulmonary TB.
Has normal K+, Mg2+ and corrected Ca2+ at screening.

Exclusion Criteria:

Is infected with a strain of M. tuberculosis resistant to a second-line injectables by line probe assay
Is infected with a strain of M. tuberculosis resistant to a fluoroquinolone by line probe assay
Has tuberculous meningitis or bone and joint tuberculosis
Is critically ill, and in the judgment of the investigator, unlikely to survive more than 4 months
Is known to be pregnant or breast-feeding
Is unable or unwilling to comply with the treatment, assessment, or follow-up schedule
Is unable to take oral medication
Has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times the upper limit of normal
Has any condition (social or medical) which in the opinion of the Investigator would make study participation unsafe
Is taking any medications contraindicated with the medicines in any trial regimen
Has a known allergy to any fluoroquinolone antibiotic
Is currently taking part in another trial of a medicinal product
Has a QT or QTcF interval at screening or immediately prior to randomisation of ≥ 450 ms.
Has experienced one or more of the following risk factors for QT prolongation:
- A confirmed prolongation of the QT or QTcF ≥ 450 ms in the screening ECG
- Pathological Q-waves (defined as Q-wave more than 40 ms or depth > 0.4-0.5 mV)
- Evidence of ventricular pre-excitation (e.g., Wolff Parkinson White syndrome)
- Electrocardiographic evidence of complete or clinically significant incomplete left bundle branch block or right bundle branch block
- Evidence of second or third degree heart block
- Intraventricular conduction delay with QRS duration > 120 ms
- Bradycardia as defined by sinus rate < 50 bpm
- Personal or family history of Long QT Syndrome
- Personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, with the exception of sinus arrhythmia
- Syncope (i.e. cardiac syncope not including syncope due to vasovagal or epileptic causes)
- Risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, or hypomagnesemia)
Has received treatment for MDR-TB in the 12 weeks prior to screening.
Has a history of cirrhosis and classified as Child's B or C at screening or a bilirubin more than 1.5 times upper limit of normal.
Has an estimated creatinine clearance < 30 mL/min (Cockcraft-Gault equation)
Is HIV positive and has a CD4 count < 50 cells/mm3
Has amylase elevation more than 2 times the upper limit of normal
Has a history of alcohol and/or drug abuse
Has had previous treatment with bedaquiline
Has taken rifampicin in the 7 days prior to randomisation
There has been a delay of more than 4 weeks between the screening consent and randomisation
Is an employee or family member of the site staff with direct involvement in the study.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02409290

Contacts


Contact: Ira David Rusen, MD	2125005720	irusen@theunion.org
Contact: Meera Gurumurthy, PhD	+65 90018835	mgurumurthy@vitalstrategies.org

Locations


China
Beijing Chest Hospital	Not yet recruiting
Beijing, China
Wuhan Institute for TB control	Not yet recruiting
Wuhan, China
Ethiopia
St. Peter's Tuberculosis Specializes Hospital	Recruiting
Addis Ababa, Ethiopia
Armauer Hanssen Research Institute	Recruiting
Adis Abbaba, Ethiopia
Georgia
JSC National Center for Tuberculosis and Lung Diseases	Not yet recruiting
Tbilisi, Georgia
India
BJ Medical College Civil Hospital	Not yet recruiting
Ahmedabad, India
The National Institute for Research in Tuberculosis	Not yet recruiting
Chennai, India
Indonesia
RSUP Persahabatan	Not yet recruiting
Jakarta, Indonesia
Moldova, Republic of
Institute of Phthisiopneumology 'Chiril Draganiuc'	Not yet recruiting
Chisinau, Moldova, Republic of
Mongolia
National Centre for Communicable Diseases	Recruiting
Ulaanbaatar, Mongolia
South Africa
King Dinizulu Hospital	Recruiting
Durban, South Africa
Helen Joseph Hospital	Recruiting
Johannesburg, South Africa
Sizwe Tropical Disease Hospital	Active, not recruiting
Johannesburg, South Africa
Doris Goodwin Hospital	Recruiting
Pietermaritzburg, South Africa
Uganda
Makerere University	Not yet recruiting
Kampala, Uganda
Mulago National Referral Hospital	Not yet recruiting
Kampala, Uganda
Vietnam
Pham Ngoc Thach Hospital	Active, not recruiting
Ho Chi Minh City, Vietnam

Sponsors and Collaborators

IUATLD, Inc

Medical Research Council

Investigators


Principal Investigator:	Sarah Meredith, MD	Medical Research Council
Principal Investigator:	Andrew Nunn, PhD	Medical Research Council

More Information

Additional Information:

Medical Research Council at UCL's web page containing information on the trial This link exits the ClinicalTrials.gov site

The International Union Against Tuberculosis and Lung Disease (study sponsor) web page containing information on the trial This link exits the ClinicalTrials.gov site

Publications:

Wells CD, Cegielski JP, Nelson LJ, Laserson KF, Holtz TH, Finlay A, Castro KG, Weyer K. HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis. 2007 Aug 15;196 Suppl 1:S86-107. Review.

Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, Rieder HL. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2010 Sep 1;182(5):684-92. doi: 10.1164/rccm.201001-0077OC. Epub 2010 May 4.

Laserson KF, Wells CD. Reaching the targets for tuberculosis control: the impact of HIV. Bull World Health Organ. 2007 May;85(5):377-81; discussion 382-6.

Zignol M, Hosseini MS, Wright A, Weezenbeek CL, Nunn P, Watt CJ, Williams BG, Dye C. Global incidence of multidrug-resistant tuberculosis. J Infect Dis. 2006 Aug 15;194(4):479-85. Epub 2006 Jul 12.

Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis: 2011 Update. Geneva: World Health Organization; 2011.

Seung KJ, Omatayo DB, Keshavjee S, Furin JJ, Farmer PE, Satti H. Early outcomes of MDR-TB treatment in a high HIV-prevalence setting in Southern Africa. PLoS One. 2009 Sep 25;4(9):e7186. doi: 10.1371/journal.pone.0007186.

Chiang CY, Enarson DA, Yu MC, Bai KJ, Huang RM, Hsu CJ, Suo J, Lin TP. Outcome of pulmonary multidrug-resistant tuberculosis: a 6-yr follow-up study. Eur Respir J. 2006 Nov;28(5):980-5. Epub 2006 Jul 12.

Mitnick C, Bayona J, Palacios E, Shin S, Furin J, Alcántara F, Sánchez E, Sarria M, Becerra M, Fawzi MC, Kapiga S, Neuberg D, Maguire JH, Kim JY, Farmer P. Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru. N Engl J Med. 2003 Jan 9;348(2):119-28.

Leimane V, Riekstina V, Holtz TH, Zarovska E, Skripconoka V, Thorpe LE, Laserson KF, Wells CD. Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study. Lancet. 2005 Jan 22-28;365(9456):318-26.

Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, Moll AP, Gandhi NR, Galvani AP. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis. 2009 Mar;9(3):153-61. doi: 10.1016/S1473-3099(09)70041-6. Review.

Diacon AH, Donald PR, Pym A, Grobusch M, Patientia RF, Mahanyele R, Bantubani N, Narasimooloo R, De Marez T, van Heeswijk R, Lounis N, Meyvisch P, Andries K, McNeeley DF. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob Agents Chemother. 2012 Jun;56(6):3271-6. doi: 10.1128/AAC.06126-11. Epub 2012 Mar 5.

Mann G, Squire SB, Bissell K, Eliseev P, Du Toit E, Hesseling A, Nicol M, Detjen A, Kritski A. Beyond accuracy: creating a comprehensive evidence base for TB diagnostic tools. Int J Tuberc Lung Dis. 2010 Dec;14(12):1518-24.

Johnson JL, Hadad DJ, Boom WH, Daley CL, Peloquin CA, Eisenach KD, Jankus DD, Debanne SM, Charlebois ED, Maciel E, Palaci M, Dietze R. Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis. 2006 Jun;10(6):605-12.

Lancioni GE, Coninx F, Smeets PM. A classical conditioning procedure for the hearing assessment of multiply handicapped persons. J Speech Hear Disord. 1989 Feb;54(1):88-93.

Cegielski JP, Dalton T, Yagui M, Wattanaamornkiet W, Volchenkov GV, Via LE, Van Der Walt M, Tupasi T, Smith SE, Odendaal R, Leimane V, Kvasnovsky C, Kuznetsova T, Kurbatova E, Kummik T, Kuksa L, Kliiman K, Kiryanova EV, Kim H, Kim CK, Kazennyy BY, Jou R, Huang WL, Ershova J, Erokhin VV, Diem L, Contreras C, Cho SN, Chernousova LN, Chen MP, Caoili JC, Bayona J, Akksilp S; Global Preserving Effective TB Treatment Study (PETTS) Investigators. Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis. Clin Infect Dis. 2014 Oct 15;59(8):1049-63. doi: 10.1093/cid/ciu572. Epub 2014 Jul 23.

Fox GJ, Menzies D. A Review of the Evidence for Using Bedaquiline (TMC207) to Treat Multi-Drug Resistant Tuberculosis. Infect Dis Ther. 2013 Dec;2(2):123-44. doi: 10.1007/s40121-013-0009-3. Epub 2013 Aug 2.

McClure N, Dornal JC. Early identification of placenta praevia. Br J Obstet Gynaecol. 1990 Oct;97(10):959-61.

Hillemann D, Rüsch-Gerdes S, Richter E. Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin-capreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol. 2009 Jun;47(6):1767-72. doi: 10.1128/JCM.00081-09. Epub 2009 Apr 22.

Mohamed K, Embleton A, Cuffe RL. Adjusting for covariates in non-inferiority studies with margins defined as risk differences. Pharm Stat. 2011 Sep-Oct;10(5):461-6. doi: 10.1002/pst.520.

Gumbo T, Louie A, Deziel MR, Parsons LM, Salfinger M, Drusano GL. Selection of a moxifloxacin dose that suppresses drug resistance in Mycobacterium tuberculosis, by use of an in vitro pharmacodynamic infection model and mathematical modeling. J Infect Dis. 2004 Nov 1;190(9):1642-51. Epub 2004 Sep 24. Erratum in: J Infect Dis. 2004 Dec 1;190(11):2059.

Falagas ME, Rafailidis PI, Rosmarakis ES. Arrhythmias associated with fluoroquinolone therapy. Int J Antimicrob Agents. 2007 Apr;29(4):374-9. Epub 2007 Jan 22. Review.

Altin T, Ozcan O, Turhan S, Ongun Ozdemir A, Akyurek O, Karaoguz R, Guldal M. Torsade de pointes associated with moxifloxacin: a rare but potentially fatal adverse event. Can J Cardiol. 2007 Sep;23(11):907-8.

Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs. 2002;62(11):1649-71. Review.

Florian JA, Tornøe CW, Brundage R, Parekh A, Garnett CE. Population pharmacokinetic and concentration--QTc models for moxifloxacin: pooled analysis of 20 thorough QT studies. J Clin Pharmacol. 2011 Aug;51(8):1152-62. doi: 10.1177/0091270010381498. Epub 2011 Jan 12.

Tsikouris JP, Peeters MJ, Cox CD, Meyerrose GE, Seifert CF. Effects of three fluoroquinolones on QT analysis after standard treatment courses. Ann Noninvasive Electrocardiol. 2006 Jan;11(1):52-6.

Sherazi S, DiSalle M, Daubert JP, Shah AH. Moxifloxacin-induced torsades de pointes. Cardiol J. 2008;15(1):71-3.

Dale KM, Lertsburapa K, Kluger J, White CM. Moxifloxacin and torsade de pointes. Ann Pharmacother. 2007 Feb;41(2):336-40. Epub 2007 Feb 6.

Rubinstein E, Camm J. Cardiotoxicity of fluoroquinolones. J Antimicrob Chemother. 2002 Apr;49(4):593-6. Review.

Morganroth J, Dimarco JP, Anzueto A, Niederman MS, Choudhri S; CAPRIE Study Group. A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia. Chest. 2005 Nov;128(5):3398-406.

Démolis JL, Kubitza D, Tennezé L, Funck-Brentano C. Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects. Clin Pharmacol Ther. 2000 Dec;68(6):658-66.

Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther. 2003 Apr;73(4):292-303.

Sacco F, Spezzaferro M, Amitrano M, Grossi L, Manzoli L, Marzio L. Efficacy of four different moxifloxacin-based triple therapies for first-line H. pylori treatment. Dig Liver Dis. 2010 Feb;42(2):110-4. doi: 10.1016/j.dld.2009.05.013. Epub 2009 Oct 28.

Stass H, Dalhoff A, Kubitza D, Schühly U. Pharmacokinetics, safety, and tolerability of ascending single doses of moxifloxacin, a new 8-methoxy quinolone, administered to healthy subjects. Antimicrob Agents Chemother. 1998 Aug;42(8):2060-5.

Alffenaar JW, de Vries PM, Luijckx GJ, van Soolingen D, van der Werf TS, van Altena R. Plasma and cerebrospinal fluid pharmacokinetics of moxifloxacin in a patient with tuberculous meningitis. Antimicrob Agents Chemother. 2008 Jun;52(6):2293-5. doi: 10.1128/AAC.01637-07. Epub 2008 Mar 24.

Soliman EZ, Lundgren JD, Roediger MP, Duprez DA, Temesgen Z, Bickel M, Shlay JC, Somboonwit C, Reiss P, Stein JH, Neaton JD; INSIGHT SMART Study Group. Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations. AIDS. 2011 Jan 28;25(3):367-77. doi: 10.1097/QAD.0b013e328341dcc0.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Moodley R, Godec TR; STREAM Trial Team. Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials. Eur Respir Rev. 2016 Mar;25(139):29-35. doi: 10.1183/16000617.0080-2015. Review.


Responsible Party:	IUATLD, Inc
ClinicalTrials.gov Identifier:	NCT02409290 History of Changes
Other Study ID Numbers:	78372190
Study First Received:	March 31, 2015
Last Updated:	July 3, 2017

Additional relevant MeSH terms:


Tuberculosis Tuberculosis, Multidrug-Resistant Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Moxifloxacin Levofloxacin Ofloxacin Isoniazid Pyrazinamide Ethambutol Clofazimine Bedaquiline Diarylquinolines	Kanamycin Prothionamide Norgestimate, ethinyl estradiol drug combination Antitubercular Agents Anti-Bacterial Agents Anti-Infective Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Contraceptives, Oral, Combined Contraceptives, Oral Contraceptive Agents, Female Contraceptive Agents

ClinicalTrials.gov processed this record on July 17, 2017

To Top