Overview

An Open-label RCT to Evaluate a New Treatment Regimen for Patients With Multi-drug Resistant Tuberculosis

Status:
Completed
Trial end date:
2021-08-30
Target enrollment:
0
Participant gender:
All
Summary
This study aims to evaluate the impact of a new injection-free six-to-nine month treatment regimen of linezolid, bedaquiline, levofloxacin, pyrazinamide (PZA) and ethionamide/high dose isoniazid (INH) compared to the conventional empiric injection-based regimen. The secondary aim is to determine if other treatment-related outcomes including adverse events, adherence to treatment, culture conversion, and cure/completion are significantly different in the intervention and conventional arms.
Phase:
Phase 2/Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Cape Town
Collaborators:
University of Cape Town Lung Institute
University of Limpopo
University of Stellenbosch
Walter Sisulu University
Treatments:
Bedaquiline
Ethionamide
Isoniazid
Kanamycin
Levofloxacin
Linezolid
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Ofloxacin
Pyrazinamide
Criteria
Inclusion Criteria:

- Newly diagnosed culture and/or GeneXpert positive pulmonary TB.

- Rifampicin resistance detected using at least two susceptibility testing assays
(GeneXpert, HainMTBDRplus or phenotypic) using a sputum sample during screening.

- Provide written informed consent prior to all trial-related procedures including HIV
testing.

- Male or female aged 18 years and older.

- Body weight between 40 and 90 kg, inclusive.

- Women of non-childbearing potential or participants of either sex who are using or
willing to use effective methods of birth control

Exclusion Criteria:

- A participant who in the opinion of the investigator is unlikely to cope with regular
visits to the trial site either because of travel constraints, or because of drug or
alcohol abuse, or other reason.

- Known at screening to have XDR-TB or pre-XDR-TB (i.e. fluoroquinolone or second-line
injectable drug (SLID) resistance i.e. to capreomycin, amikacin and kanamycin).

- Previous history of treatment for MDR-TB or XDR-TB or previous treatment with
bedaquiline.

- Currently on MDR-TB treatment for more than 2 weeks.

- Any participant with a Karnofsky score < 50.

- Known allergy to any of the trial drugs or related substances.

- Having participated in other clinical studies within 8 weeks prior to trial start
where investigational agents were used that may potentially impact current trial
outcome.

- Presence (or evidence) of symptomatic neuropathy grade 3 or higher.

- Epilepsy where drugs prolonging QT interval are used.

- Participant who is pregnant, breast-feeding (and not willing to stop), or planning to
conceive a child within 6 months of cessation of treatment.

- Incompatibility between microbiological and clinical/ radiological findings (i.e.
where the clinical and/or radiological findings are discordant with microbiological
testing suggesting laboratory contamination).

- Participants with ECG abnormalities, in particular QT prolongation.

- Any pre-existing laboratory abnormality which in the opinion of the investigator will
place the participant at risk. Patients with any of the following baseline laboratory
abnormalities will be excluded from the study:

- Creatinine grade 2 or worse (>1.4 times ULN)

- Hemoglobin level grade 4 (HB <6.5g/dL)

- Platelets grade 3 or worse (<49999 x 109/L)

- ALT grade 3 or worse (>5 times ULN)

- Total bilirubin grade 3 or worse (>2.5 times ULN)

- Specific prior or concurrent medication/treatments (see Restrictions section below,
Table 3).

- Rifampicin monoresistant TB.

- Fluoroquinolone and/or SLID resistance. Although in South Africa, the standard of care
does not single out MDR-TB with fluoroquinolone or aminoglycoside resistance at
initiation of MDR-TB treatment, in this study the Hain MTBDRsl LPA will be used on the
sputum sample to exclude any pre-XDR and XDR cases from participation in the study
(results from the LPA and phenotypic DST testing on the isolate will be available 3-6
weeks later).

All inclusion and no exclusion criteria must be met prior to enrolment and randomisation.
Whenever the investigator has reason to suspect that there might be a health problem (other
than TB) participation should only be considered after discussing the case with the medical
monitor. Note: Participants who are currently on, or have previously been on drug-sensitive
TB treatment are not excluded from participation.

Post-randomisation exclusion criteria:

• Fluoroquinolone and/or SLID resistance detected on DST using the isolate. Note: A woman
who falls pregnant during the treatment phase of the trial will not be excluded but will be
counselled regarding potential termination of pregnancy.