Tuberculosis Clinical Trial
— NEXTOfficial title:
Evaluating a New Treatment Regimen for Patients With Multidrug-resistant TB (MDR-TB) - a Prospective Open-label Randomised Controlled Trial
Verified date | September 2021 |
Source | University of Cape Town |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 154 |
Est. completion date | August 30, 2021 |
Est. primary completion date | December 31, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
South Africa | Brooklyn Chest Hospital | Cape Town | Western Cape |
Lead Sponsor | Collaborator |
---|---|
University of Cape Town | University of Cape Town Lung Institute, University of Limpopo, University of Stellenbosch, Walter Sisulu University |
South Africa,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Treatment success | In the conventional arm treatment success is defined as the sum of cured or treatment completed cases. In the intervention arm treatment success is defined as the sum of cured and treatment completed cases, without subsequent relapse, re-infection or death during the 15-18 month follow up period. | 24 months after initiation of treatment in either arm. | |
Secondary | Favourable outcome rate | At 6-9 months for the intervention arm and 21-24 months for the conventional arm. | ||
Secondary | Time specific rate of treatment failure. | 6-36 months | ||
Secondary | Time specific culture conversion proportions and rates. | 6-36 months | ||
Secondary | Time specific relapse rate. | 6-36 months. | ||
Secondary | Rate of re-infection. | 6-36 months. | ||
Secondary | All cause mortality | 0-36 months. | ||
Secondary | Composite measure of QT interval on ECG, grade 3 and 4 adverse events, stopping drugs Safety and tolerability end-points. | 0-36 months. | ||
Secondary | Default rate | Rate at which participants interrupt treatment for two or more consecutive months for any reason without medical approval. | 2-24 months | |
Secondary | Rate of loss of follow-up. | Rate at which a participant becomes untraceable at any point in the study, and remains untraceable at completion of study despite every effort being made by researchers to locate the participant. | 0-36 months. |
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