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.: PACTR201811667026997 Date of Registration: 12/11/2018
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Test to Treat TB: Impact of sputum sequencing-guided individualised therapy on outcomes in drug-resistant tuberculosis (TB): a proof of concept randomised controlled trial
Official scientific title Test to Treat TB: Impact of sputum sequencing-guided individualised therapy on outcomes in drug-resistant tuberculosis (TB): a proof of concept randomised controlled trial
Brief summary describing the background and objectives of the trial Precision medicine to guide individualised therapy is the next major paradigm shift for TB care of drug-resistant disease and is already adopted in some high income settings11. Thus, we propose that the right drug, at the right dose, be given in the specific context like in diseases such as diabetes and hypertension. It would be strange and medically indefensible to empirically treat hypertension or diabetes without context-specific individualisation; so why so we do so for TB? This project is the first study of its kind to investigate the impact of rapid drug resistance profiling and tailored treatment on patient outcomes in a TB endemic country. We expect to show that sequencing-guided individualised therapy significantly reduces the time taken for patients to start effective therapy (at least 5 likely effective drugs). The timing is ripe to test this approach for detecting resistance as sequencers are now available in clinical laboratories (often for diseases like cancer), and bench top rapid sequencing is a reality (Illumina iSeq 100 and Oxford Nanopore devices). If this proof of concept trial demonstrates a significant impact on outcomes, then it will be a major driver for investment into molecular profiling to guide individualised therapy for DR-TB Primary outcome measurement: • Stage 1 outcome measurement: Treatment initiation with at least 5 likely effective drugs within 14 days of diagnosis of rifampicin resistance. • Stage 2 outcome measurement: Six-month favourable outcome rate. • Stage 3 outcome measurement: Twelve-month favourable outcome rate (overall primary outcome measure for the trial and at the end of stage 3). Secondary outcomes measurements: • Six-month culture conversion rates • Time to and rate of culture conversion • Change in TB related morbidity over 6 months • Amplification of drug resistance • Time-point specific micro-hetero-resistance rates • Accuracy and time to result of each resistance detection strategy. • Feasibility
Type of trial RCT
Acronym (If the trial has an acronym then please provide) T3RCT
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Diagnosis / Prognosis
Anticipated trial start date 07/01/2019
Actual trial start date
Anticipated date of last follow up 31/12/2019
Actual Last follow-up date
Anticipated target sample size (number of participants) 280
Actual target sample size (number of participants)
Recruitment status Not yet 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 Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Standard of care Standard of care for the treatment of rifampicin resistant tuberculosis Diagnose and treat with five effective drugs against rifampicin tuberculosis 140 Active-Treatment of Control Group
Experimental Group Individulised treatment group 9-11 months At least five effective drugs available from the National Tuberculosis Control Programme (NTP) commenced within14 days based on targeted genome sequencing 140
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Newly diagnosed culture and/or Xpert/MTB Ultra positive pulmonary TB • Rifampicin mono-resistance detected using the results from two susceptibility-testing assays (GeneXpert, HainMTBDRplus or phenotypic DST). This will be done on a sputum sample during screening, or with pre-existing results available from the local health care service. • Provide written informed consent prior to all trial-related procedures • Male or female aged 18 years and older. • Patients on TB treatment for less then 8 days. • A subject who in the opinion of the investigator is unlikely to cope with regular visits to the trial site either because of travel constraints, or drug or alcohol abuse, or other reason. • Currently on MDR-TB treatment for more than 2 weeks. • Any participant with a clinically significant medical condition that, in the opinion of the investigator, may be negatively affected by the patient’s participation in the study. • Any subject with a Karnofsky score < 50. • 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. • Participant who is pregnant, breast-feeding (and not willing to stop), or planning to conceive a child within 6 months of cessation of treatment. • Any pre-existing laboratory abnormality, which in the opinion of the investigator will place the participant at risk (see detailed protocol for grade of abnormality). 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 80 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
No 07/11/2018 UCT ethics committee
Ethics Committee Address
Street address City Postal code Country
Floor E53, Room 46 Old Main Building Groote Schuur Hospital Observatory, 7925 Cape Town 7925 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Treatment initiation with at least 5 likely effective drugs within 14 days of diagnosis of rifampicin resistance 14 days
Primary Outcome Six-month favourable outcome rate. 6 months
Primary Outcome Twelve-month favourable outcome rate (overall primary outcome measure for the trial and at the end of stage 3 12 month
Secondary Outcome Six-month culture conversion rates 6 months
Secondary Outcome Time to and rate of culture conversion negative consecutive cultures
Secondary Outcome Change in TB related morbidity over 6 months 6 months
Secondary Outcome Amplification of drug resistance 6 months
Secondary Outcome Time-point specific micro-hetero-resistance rates in each group 6 months
Secondary Outcome Accuracy and time to result of each resistance detection strategy 6 months
Secondary Outcome Feasibility, practicality, scalability and cost 12 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Brooklyn Chest Hospital Stanberry St, Ysterplaat Cape Town 7405 South Africa
Don McKenzie Hospital 10 Zulu Reserve Rd Durban 3660 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
UCT Lung Institute George St, Mowbray Cape Town 7700 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor UCT Lung Institute George St, Mowbray Cape Town 7700 South Africa Individual
COLLABORATORS
Name Street address City Postal code Country
Rob Warren P8, Fisan Building, Tygerberg Medical Campus, Francie van Zil Drive, Tygerberg Hospital Cape Town 7505 South Africa
Dave Engelthaler TGen headquarters 445 N. Fifth Street Phoenix, AZ 85004 Arizona 85004 United States of America
David Dowdy 615 N Wolfe St, Baltimore, Maryland 21205 United States of America
Nazir Ismail 1 Modderfontein Road Sandringham Johannesburg 2131 South Africa
Tawanda Gumbo 3310 Live Oak St Suite Dallas 75204 United States of America
Simon Travis 42 Hans Strijdom Ave Ln, Cape Town City Centre Cape Town 8000 South Africa
Helen Cox IDM, Anzio Road Cape Town 7925 South Africa
Mark Nicol Anzio Road cape Town 7925 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Keertan Dheda keertan.dheda@uct.ac.za 0214062000 George St, Mowbray
City Postal code Country Position/Affiliation
Cape Town 7700 South Africa Head of Pulmonology
Role Name Email Phone Street address
Scientific Enquiries Jason Limberis jason.limberis@uct.ac.za 0214062000 George St, Mowbray
City Postal code Country Position/Affiliation
Cape Town 7700 South Africa Research fellow
Role Name Email Phone Street address
Public Enquiries ali esmail a.esmail@sun.ac.za 021406119 George St, Mowbray
City Postal code Country Position/Affiliation
Cape Town 7700 South Africa Clinical Trial Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Undecided
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