Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial

Table 3 Study timeline for control arm

	Screening	Baseline visit^a	Treatment						End of treatment^g (End of study)
Weeks (w)	–2 w ~ –1 day	0	1 w	2 w	4 w	8 w	12 w ~ (every 4w)	52 w ~ (every 2 months)	80 w ~ 24 months
Visit window	NA	NA	± 4 days	± 4 days	± 1w	± 2w	± 2 w	± 2 w	± 2 w
Consent	X
Randomization		X
Medical history	X
Physical exam	X		X	X	X	X	X	X	X
Neurological exam	X
Sputum AFB smear	X ^e	X ^e	X	X	X	X	X	X	X
TB culture (solid)	X ^e	X ^e	X	X	X	X	X	X	X
TB culture (liquid)	X ^e	X ^e	X	X	X	X	X	X	X
Genotypic DST	If available
Phenotypic DST^b	With first/reverted cultured Mycobacterium tuberculosis
CXR	X ^e	X ^e	X ^h	X ^h	X	X	X	X	X
Chemistry, electrolytes	X ^e	X ^e	X	X	X	X	X	X	X
Complete blood count	X ^e	X ^e	X	X	X	X	X	X	X
ECG	X ^e
Urine HCG^c	X	X
HIV, HBV^d		X ^e
Optic test	X
Compliance of drug intake			X	X	X	X	X	X	X
Adverse drug reaction			X	X	X	X	X	X	X
Other medication^f	X	X	X	X	X	X	X	X	X

AFB acid-fast bacilli, CXR chest x-ray, DST drug susceptibility testing, ECG electrocardiogram, HBV hepatitis B virus, HCG human chorionic gonadotropin, HIV human immunodeficiency virus, NA not applicable, TB tuberculosis
^aAdministration of anti-TB regimen can begin at baseline visit since drug-resistant TB must be treated immediately
^bDrug susceptibility test for isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, kanamycin, amikacin, capreomycin, ofloxacin, levofloxacin, moxifloxacin, prothionamide, cycloserine, and p-aminosalicylic acid (can be omitted for patients with results already provided)
^cOnly in females of childbearing potential (blood HCG test results are available)
^dStudy drugs can be administered before obtaining the results since eligibility is not determined by these results
^eCan be omitted if previous tests except ECG were done within 4 weeks. In case of ECG, within 1 week
^fCheck prohibited drugs for exclusion criteria at screening visit and check immunosuppressants including steroids after enrollment
^gEnd of treatment visit will be determined by the time of culture conversion
^hCan be omitted if previous test was done within 2 weeks

ISSN: 1745-6215