Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202203645724919 Date of Approval: 15/03/2022
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Safety, effectiveness, and feasibility of a short and all-oral treatment regimen for the treatment of rifampicin-resistant tuberculosis in Niger
Official scientific title Safety, effectiveness, and feasibility of a short and all-oral treatment regimen for the treatment of rifampicin-resistant tuberculosis in Niger
Brief summary describing the background and objectives of the trial The treatment of rifampicin-resistant tuberculosis (RR-TB), TB resistant to the most powerful anti-TB drug, requires a more complex regimen than the treatment of rifampicin-susceptible TB and more frequently causes severe adverse drug reactions. In Niger, during the past 10 years, the RR-TB treatment strategy was highly successful, with 83% relapse-free cure. RR-TB patients are treated with a second line injectable drugs (SLID) containing short treatment regimen (STR). The STR’s SLID is replaced by linezolid (LZD) in patients with ototoxicity. Audiometry is done at baseline and on a monthly basis during treatment. As any audiometry abnormality serves as indication for switching to LZD, not a single RR-TB patients developed severe hearing loss since 2017. Bedaquiline (BDQ) is safeguarded for the rare patients with treatment failure or relapse after a first STR, leaving not a single patient without treatment option. Since 2020 WHO recommends constituting all-oral STR, thus replacing the SLID by bedaquiline. WHO also recommends research on STR using both BDQ and LZD in patients who have not yet taken second-line drugs for more than one month and for whom fluoroquinolone resistance has been ruled out. Considering the highly effective RR-TB treatment strategy used in Niger, it was not justified to introduce the WHO BDQ/LZD-containing STR without a rigorous evaluation. We therefore aim to compare the safety, effectiveness and feasibility of the WHO all-oral BDQ/LZD-containing STR (experimental arm) with the Niger RR-TB treatment strategy, using a SLID-containing regimen, with LZD replacing the SLID in case of ototoxicity (control arm). To provide high-level evidence on the one hand, but also timely inform local and international guidelines, we used an approach that would be feasible for the local RR-TB programme. We designed a pragmatic randomized clinical trial with stratified block randomization, using month of RR-TB diagnosis as stratifying variable.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 15/04/2021
Actual trial start date
Anticipated date of last follow up 15/01/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 230
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group The control arm 9 to 11 months The control arm relies on the Niger RR-TB treatment strategy. It relies on the national 9-11 month standard RR-TB STR, which includes moxifloxacin (MFX), clofazimine (CFZ), ethambutol (E), and pyrazinamide (Z) throughout, supplemented by a SLID (amikacin), prothionamide (PTO) and high-dose isoniazid (Hh; 10mg/kg) during the first 4 months (6 months if delayed conversion on smear microscopy at treatment month 4). The SLID is replaced with LZD in case of any hearing disturbance detected on audiometry (4-6 SLID-Hh-PTO-MFX-CFZ-E-Z/5 MFX-CFZ-E-Z, with LZD replacing the SLID in case of any hearing disturbance detected on audiometry, at baseline or during treatment). 115 Active-Treatment of Control Group
Experimental Group The experimental arm 9 to 11 months The experimental arm uses the WHO all-oral regimen, which contains LZD, high-dose isoniazid, prothionamide, high-dose levofloxacin (LFXh), BDQ, CFZ and pyrazinamide for 4 months (6 months if delayed conversion on smear microscopy at treatment month 4), followed by 5 months of treatment with high-dose levofloxacin, BDQ, CFZ and pyrazinamide (4-6 LZD-Hh-PTO-LFXh-BDQ-CFZ-Z/5 LFXh-BDQ-CFZ-Z). 115
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1) have bacteriologically confirmed TB with evidence of resistance to rifampicin (for children the diagnosis is not always bacteriologically confirmed as the RR-TB diagnosis may be based on clinical TB diagnosis plus history of a close contact with a confirmed RR-TB case) and susceptibility to fluoroquinolones and 2) be willing and able to give informed consent to participate in the study (signed or witnessed consent if the patient is illiterate; signed or witnessed consent by a child's parent or legal guardian). 1) previous treatment for more than one month with second-line TB drugs included in the to be evaluated treatment regimens, 2) a QTcF interval ≥ 500 msec at baseline that is not corrected by medical management, 3) any other medical contraindications for taking the study regimens, 4) being younger than 6 years old, and 5) diabetes mellitus. 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s) 6 Year(s) 90 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/04/2021 COMITE NATIONAL D ETHIQUE POUR LA RECHERCHE EN SANTE
Ethics Committee Address
Street address City Postal code Country
MINISTERE DE SANTE PUBLIQUE DE LA POPULATION ET DES AFFAIRES SOCIALES NIAMEY 163 Niger
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/03/2021 COMITE VOOR MEDISCHE ETHIEK
Ethics Committee Address
Street address City Postal code Country
UZA / WILRIJKSTRAAT 10 / 2650 EDEGEM EDEGEM 2650 Belgium
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/01/2021 INSTITUTIONAL REVIEW BOARD
Ethics Committee Address
Street address City Postal code Country
NATIONALESTRAAT 155 ANTWERP 2000 Belgium
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome any grade 3-5 adverse event The maximum grade measured up to 6 months after the end of treatment.
Secondary Outcome Treatment success without relapse 12 months after the end of treatment 12 months after the end of treatment
Secondary Outcome Ninety percent of doses of RR-TB treatment taken end of treatment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
RR TB unit of Niamey Unite TB MR de Niamey, centre national de lutte contre la tuberculose et les maladies respiratoires, ex CNAT Niamey Niger
RR TB unit of Maradi Unite TB MR de Maradi CHR Maradi Maradi Niger
RR TB unit of Tahoua Unite TB MR de Tahoua CHR Tahoua Tahoua Niger
RR TB unit of Zinder Unite TB MR de Zinder, Hopital National de Zinder Zinder Niger
FUNDING SOURCES
Name of source Street address City Postal code Country
DAMIEN FOUNDATION Rue Kouara Kano 37, porte 672 NIAMEY 1065 Niger
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor DAMIEN FOUNDATION Rue Kouara Kano 37, porte 672 NIAMEY 1065 Niger Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Institute of tropical medecine Antwerp Nationalestraat 155 ANTWERP 2000 Belgium
PROGRAMME NATIONAL DE LUTTE CONTRE LA TUBERCULOSE MINISTERE DE LA SANTE PUBLIQUE DE LA POPULATION ET DES AFFAIRES SOCIALES NIAMEY Niger
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator MAHAMADOU BASSIROU SOULEYMANE bachirsoul@gmail.com +2279697985157 Rue Kouara Kano 37, porte 672
City Postal code Country Position/Affiliation
NIAMEY Niger NTP medical advisor
Role Name Email Phone Street address
Scientific Enquiries TOM DECROO tdecroo@itg.be +32489271771 Nationalestraat 155
City Postal code Country Position/Affiliation
ANTWERP Belgium Researcher
Role Name Email Phone Street address
Public Enquiries ALBERTO PIUBELLO albertopiubello@yahoo.it +393453079647 Bd Leopold II 263
City Postal code Country Position/Affiliation
BRUSSELLS Belgium Medical Advisor
Role Name Email Phone Street address
Principal Investigator ALPHAZAZI SOUMANA s_alphazazi@yahoo.fr +22799446767 PROGRAMME NATIONAL DE LUTTE CONTRE LA TUBERCULOSE
City Postal code Country Position/Affiliation
NIAMEY Niger NTP National Coordinator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in this article, after de identification (text, tables, figures, and appendices) Informed Consent Form,Study Protocol After publication of the main findings After approval of the principal investigator
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information