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CompletedNCT05452616SaDAPTUpdated Apr 4, 2025

Same-day Versus Rapid ART Initiation in HIV-positive Individuals Presenting With Symptoms of Tuberculosis

An interventional study of ART first- Therapeutic use trial and TB results first- Therapeutic use trial in Human Immunodeficiency Virus (HIV) Infection, sponsored by University Hospital, Basel, Switzerland. Completed at 2 sites in 2 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2025-04-04.

Sponsored by University Hospital, Basel, Switzerland · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
610
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study summary

SaDAPT is a pragmatic, randomized, therapeutic-use trial comparing two approaches ("ART first" versus "TB results first") for the timing of ART initiation in PLHIV with presumptive TB, but no signs of central nervous system (CNS) disease, in a routine primary and secondary care setting in southern Africa with regard to HIV viral suppression (VL \<400 copies/mL) 26 weeks after enrolment.

Read the detailed description

In this randomized controlled trial (RCT) two different, guideline-approved algorithms for antiretroviral therapy (ART) initiation in people living with HIV (PLHIV) with presumptive Tuberculosis (TB), but no signs of central nervous system (CNS) disease will be compared. In one arm, same-day initiation (SDI) of ART will be applied ("ART first") for all participants independent of the status or results of initial TB investigations. In the other arm, an approach with deferral of ART initiation until TB is excluded or confirmed and TB treatment initiated will be applied ("TB results first"). The direct comparison of the two approaches in a pragmatic, two-country RCT conducted in a representative high-prevalence setting will provide evidence on the open question of optimal timing of ART initiation in the large subgroup of PLHIV with presumptive TB outside the CNS.

02

Conditions studied

  • Human Immunodeficiency Virus (HIV) Infection

Keywords

  • Tuberculosis (TB) infection
  • Acquired immunodeficiency syndrome
  • Antiretroviral therapy (ART)
  • Immune reconstitution inflammatory syndrome
  • People living with HIV (PLHIV)
  • Same-day initiation (SDI) of ART
  • TB preventive treatment
  • Sub-Saharan African countries
  • HIV/TB-coinfection
  • immune reconstitution inflammatory syndrome (IRIS)
03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 12 years or older
  • HIV-positive
  • Not taking ART (naïve or reported no ART intake since 90 days or more)
  • Presenting with one or more TB symptoms according to W4SS
  • Unknown TB status
  • Planning to continue care at the study facility for at least 30 weeks
  • Willing and able to consent (age 18 years or older) or assent with guardian consent (age 12 to 17 years)

Exclusion criteria

Exclusion Criteria:

  • Medical condition requiring admission or referral to a higher level health facility at enrolment
  • Symptoms or clinical signs suggestive for diseases of the CNS
  • Positive cryptococcal antigen test (CrAg)
  • Reporting to be pregnant
  • Taking TB treatment, TB preventive therapy (TPT) or treatment against cryptococcal meningitis
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
610 participants (actual)

Study arms

  • Active comparator
    "ART first" arm

    ART initiation on the day of enrolment independent of TB investigations

    Other: ART first- Therapeutic use trial

  • Active comparator
    "TB results first" arm

    ART initiation only after active TB has been refuted or confirmed

    Other: TB results first- Therapeutic use trial

Interventions

  • OtherART first- Therapeutic use trial

    ART initiation on the day of enrolment independent of TB investigations in PLHIV with presumptive TB but no signs of CNS disease. The trial uses treatments and drug-doses as per international and national guidelines. All treatment components will be applied at standard dosage and no new substances or alternative indications will be tested.

  • OtherTB results first- Therapeutic use trial

    Deferral of ART initiation until active TB has been refuted or confirmed. PLHIV presenting with symptoms (cough, fever, night sweat, weight loss) are defined as presumptive TB, and should have microbiological TB investigations. Routine TB investigations in Malawi and Lesotho usually consist of two sputum bottles for analysis using nucleic acid amplification tests (Xpert MTB/RIF (Ultra)).The trial uses treatments and drug-doses as per international and national guidelines. All treatment components will be applied at standard dosage and no new substances or alternative indications will be tested.

05

What researchers measure

Primary outcomes

  1. HIV viral suppression <400 copies/mL

    HIV viral suppression \<400 copies/mL (obtained from routine laboratory reports at study facility, from laboratory reports of referral facility in case of transfer out, or from dried blood spot (DBS) sample for participants without documented clinic visit but found during home visit tracing)

    Time frame: 26 (22 - 40) weeks after enrolment

Secondary outcomes

  1. Retention in care

    Retention in care, defined as a documented ART clinic visit between 22 and 30 weeks after enrolment

    Time frame: 26 (22 - 30) weeks after enrolment

  2. Engagement in care

    Engagement in care, defined as reporting regular ART intake, irrespective if a documented visit took place between 22 and 30 weeks after enrolment

    Time frame: 26 (22 - 30) weeks after enrolment

  3. Disengagement from care

    Disengagement from care, defined as non-engaged in care but reached through patient tracing

    Time frame: 26 (22 - 30) weeks after enrolment

  4. Lost to follow-up

    Lost to follow-up, defined as non-retained in care and not reached through tracing

    Time frame: 26 (22 - 30) weeks after enrolment

  5. Non-traumatic mortality

    Non-traumatic mortality

    Time frame: during the first 30 weeks after enrolment

  6. Serious adverse events (SAEs)

    SAEs

    Time frame: during the first 30 weeks after enrolment

  7. TB-Immune reconstitution inflammatory syndrome (IRIS)

    TB-Immune reconstitution inflammatory syndrome (IRIS) is defined as Adverse event of special interest (AESIs): AESIs

    Time frame: during the first 30 weeks after enrolment

  8. Incidence of TB disease (microbiologically confirmed and/or clinical diagnosis)

    Incidence of TB disease (microbiologically confirmed and/or clinical diagnosis), defined as any TB diagnosis after enrolment not classified as prevalent TB at enrolment

    Time frame: during the first 30 weeks after enrolment

  9. HIV viral suppression

    HIV viral suppression using different thresholds (\<20 copies/mL; \<100 copies/mL; \<1000 copies/mL)

    Time frame: at 26 (22 - 40) weeks

Other outcomes

  1. Prevalence of active TB diagnosed at enrolment (exploratory endpoint)

    Prevalence of active TB, defined as TB diagnosed clinically or microbiologically through the TB investigations at enrolment

    Time frame: up to a maximum of 28 days after enrolment

06

Study locations

2 sites
  • SolidarMed Lesotho, Premium House #224, Kingsway, Maseru West
    Maseru, Lesotho
  • Kamuzu University of Health Sciences, Helse Nord Tuberculosis Initiative
    Blantyre, Malawi
07

References and documents

Study documents

  • Study protocol · Feb 14, 2023
  • Statistical analysis plan · Jan 14, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — * An anonymized key dataset necessary for reproducing the primary and key secondary endpoints will be made freely available in an appropriate repository, such as zenodo.org, alongside the publication of the study results. Besides removal of variables not required for key analysis, we will remove participant identifier, study site and exact date information. Requests for access to more detailed data may be made to the corresponding author by submitting a proposal, which will be reviewed by the trial consortium. * The statistical report for the primary and key secondary endpoints and the code to produce it will be published together with the data set.

Supporting information: Study protocol, Sap, Icf, Analytic code

08

Registry details

Key details

Study ID
NCT05452616
Lead sponsor
University Hospital, Basel, Switzerland
Collaborators
Swiss National Science Foundation, SolidarMed, Kamuzu University of Health Sciences, Malawi, Swiss Tropical & Public Health Institute, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, London School of Hygiene and Tropical Medicine
Responsible party
Sponsor
First posted
Jul 11, 2022
Start date
Oct 19, 2022
Primary completion
Nov 26, 2024
Completion
Jan 14, 2025
Last update
Apr 4, 2025

Study contacts

Niklaus Labhardt, Prof. Dr. DTM&H, MIH
principal investigator · Division of Clinical Epidemiology, University Hospital Basel
Rachael Mary Burke, BMBCh, MSc, DTM&H
principal investigator · London School of Hygiene and Tropical Medicine

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.

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