Design and protocol for a cluster randomised trial of enhanced diagnostics for tuberculosis screening among people living with HIV in hospital in Malawi (CASTLE study).
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
24
08
2021
accepted:
16
09
2021
entrez:
10
1
2022
pubmed:
11
1
2022
medline:
17
2
2022
Statut:
epublish
Résumé
People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest. An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation. Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV.
Sections du résumé
BACKGROUND
People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest.
DESIGN AND METHODS
An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation.
DISCUSSION
Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV.
Identifiants
pubmed: 35007306
doi: 10.1371/journal.pone.0261877
pii: PONE-D-21-27191
pmc: PMC8746787
doi:
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0261877Subventions
Organisme : Wellcome Trust
ID : 200901/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206575/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M007375/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R010161/1
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Lancet. 2018 Jul 28;392(10144):292-301
pubmed: 30032978
Sci Rep. 2019 Oct 18;9(1):15000
pubmed: 31628424
Lancet. 2016 Mar 19;387(10024):1187-97
pubmed: 26970721
AIDS. 2015 Sep 24;29(15):1987-2002
pubmed: 26266773
J Int AIDS Soc. 2016 Jan 12;19(1):20714
pubmed: 26765347
BMC Med. 2017 Mar 21;15(1):67
pubmed: 28320384
Lancet HIV. 2015 Oct;2(10):e438-44
pubmed: 26423651
BMJ. 2013 Jan 08;346:e7586
pubmed: 23303884
PLoS One. 2016 Nov 9;11(11):e0166158
pubmed: 27829072
Int J Tuberc Lung Dis. 2016 Sep;20(9):1226-30
pubmed: 27510250
PLoS Med. 2020 May 1;17(5):e1003113
pubmed: 32357197
AIDS. 2021 Nov 1;35(13):2191-2199
pubmed: 34172671
Wellcome Open Res. 2018 May 18;3:61
pubmed: 30542662
Lancet Infect Dis. 2019 Aug;19(8):852-861
pubmed: 31155318
Lancet Infect Dis. 2015 May;15(5):544-51
pubmed: 25765217
Open Forum Infect Dis. 2021 Mar 31;8(7):ofab162
pubmed: 34327252