Clinical Trial Results:
The HALT-LTBI study: Phase IV, multi-site, unblinded, randomised trial of prophylactic daily rifampicin/isoniazid vs. weekly rifapentine/isoniazid for latent tuberculosis infection (LTBI)
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Summary
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EudraCT number |
2013-000750-21 |
Trial protocol |
GB |
Global end of trial date |
17 May 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Apr 2019
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First version publication date |
12 Apr 2019
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Other versions |
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Summary report(s) |
MHRA Final Study Report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
12/0426
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Additional study identifiers
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ISRCTN number |
ISRCTN04379941 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UCL
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Sponsor organisation address |
Joint Research Office, Gower Street , London , United Kingdom, WC1E 6BT
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Public contact |
Ibrahim Abubakar, University College London, +44 02076790954, i.abubakar@ucl.ac.uk
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Scientific contact |
Ibrahim Abubakar, University College London, +44 02076790954, i.abubakar@ucl.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Aug 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
17 May 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess completion rates of two different LTBI treatment regimens (daily rifampicin/isoniazid, the current UK standard treatment, vs weekly rifapentine/isoniazid).
The objective of the pilot phase would be to assess feasibility and safety.
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Protection of trial subjects |
Insurance in Place
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Dec 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 52
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Worldwide total number of subjects |
52
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EEA total number of subjects |
52
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
52
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruited individuals were randomised to receive either a daily combination of rifampicin/isoniazid (‘standard’ practice) for 90 days (three months) versus a weekly combination of rifapentine/isoniazid (‘experimental’ practice), for 12 weeks. Safety and feasibility was assessed with 52 patients. | |||||||||
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Pre-assignment
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Screening details |
The probability of being screened encompasses the probability of being offered screening (e.g. via primary care) and of accepting the offer. The number of simulations was N = 1000 which captured both the individual level variation and the uncertainty in the costs and utilities. | |||||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Experimental Treatment Arm | |||||||||
Arm description |
- | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Rifampicin/Isoniazid daily
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50 kg or less above 50 kg
3 x Rifinah® 150/100 2 x Rifinah® 300/150
All patients will receive Pyridoxine 10 mg or 25 mg* with their dose (once daily for 90 days)
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Investigational medicinal product name |
Rifampicin/Isoniazid Weekly
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
< 50 kg ≥ 50 kg
5 x Priftin® 150 mg
(Rifapentine 750 mg)
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Isoniazid 15 mg/kg
300 mg and or 150 mg oral tablets will be used, therefore:
45-50 kg = 750 mg isoniazid
6 x Priftin® 150 mg
(Rifapentine 900 mg)
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Isoniazid 15 mg/kg
300 mg and or 150 mg oral tablets will be used, therefore:
50-55 kg = 750 mg isoniazid
Above 55 – 60 kg = 900 mg isoniazid
>60 kg = 900 mg isoniazid
All patients will receive Pyridoxine 10 mg or 25 mg with their dose (once weekly for 12 weeks)*
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Arm title
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Standard Treatment Arm | |||||||||
Arm description |
- | |||||||||
Arm type |
Standard Care | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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End points reporting groups
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Reporting group title |
Experimental Treatment Arm
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Reporting group description |
- | ||
Reporting group title |
Standard Treatment Arm
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Reporting group description |
- | ||
Subject analysis set title |
Primary Outcome
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
LTBI successfully led to the recruitment of 52 participants to explore the feasibility of a full trial. Factors to improve study enrolment were identified including appropriate inclusion criteria. There was no difference in the adverse effect profile between the two arms. Economic modelling suggests that the 12 dose rifapentine based regimen may be cost-effective if it achieves the same level of effectiveness as observed in this pilot study.
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End point title |
Analysis [1] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Safety and feasibility was assessed with 52 patients. Multivariable logistic regression of the likelihood of completion of treatment and presence of adverse effects was undertaken. Likert scale-derived data from MARS-5 on treatment completion was analysed
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please refer to Final Study report for full analysis. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
To assess frequency of adverse events (AE) when individuals are treated for LTBI.
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Assessment type |
Non-systematic | ||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||
Dictionary version |
19
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Reporting groups
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Reporting group title |
Randomised Group
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Reporting group description |
- | ||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Please refer to report in attached which details the breakdown of 122 AEs that occurred on this trial. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
