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

Human Immunodeficiency Virus (HIV) Infection Clinical Trial

— SaDAPT  

Official title:

Same-day Versus Rapid ART Initiation in HIV-positive Individuals Presenting With Symptoms of Tuberculosis: an Open-label Randomized Non-inferiority Trial in Lesotho and Blantyre District, Malawi

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05452616
• Other study ID #: AO_2022-00031; am22Labhardt
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 19, 2022
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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. Serum proteome sub- study: Prediction of clinical phenotypes in people living with HIV using the serum proteome. In a laboratory-based sub-study the plasma samples and clinical data collected as part of SaDAPT trial and ART initiation cohort at the study sites in Lesotho are used. The samples are screened for circulating inflammatory markers using proteomics in PLHIV with high risk of active TB and Immune reconstitution inflammatory syndrome (IRIS). The proteome will be deconvoluted using computational biology with the aim to develop diagnostics for active TB disease and predictors for IRIS.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 611
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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:

• 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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus (HIV) Infection
• Immunologic Deficiency Syndromes
• Tuberculosis

Intervention

Other:
• ART 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.
• TB 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.

Locations

Country	Name	City	State
Lesotho	SolidarMed Lesotho, Premium House #224, Kingsway, Maseru West	Maseru
Malawi	Kamuzu University of Health Sciences, Helse Nord Tuberculosis Initiative	Blantyre

Sponsors (7)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Kamuzu University of Health Sciences, Malawi, London School of Hygiene and Tropical Medicine, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, SolidarMed Lesotho, Swiss National Science Foundation, Swiss Tropical & Public Health Institute

Countries where clinical trial is conducted

Lesotho,  Malawi, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	up to a maximum of 28 days after enrolment
Primary	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)	26 (22 - 40) weeks after enrolment
Secondary	Retention in care	Retention in care, defined as a documented ART clinic visit between 22 and 30 weeks after enrolment	26 (22 - 30) weeks after enrolment
Secondary	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	26 (22 - 30) weeks after enrolment
Secondary	Disengagement from care	Disengagement from care, defined as non-engaged in care but reached through patient tracing	26 (22 - 30) weeks after enrolment
Secondary	Lost to follow-up	Lost to follow-up, defined as non-retained in care and not reached through tracing	26 (22 - 30) weeks after enrolment
Secondary	Non-traumatic mortality	Non-traumatic mortality	during the first 30 weeks after enrolment
Secondary	Serious adverse events (SAEs)	SAEs	during the first 30 weeks after enrolment
Secondary	TB-Immune reconstitution inflammatory syndrome (IRIS)	TB-Immune reconstitution inflammatory syndrome (IRIS) is defined as Adverse event of special interest (AESIs): AESIs	during the first 30 weeks after enrolment
Secondary	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	during the first 30 weeks after enrolment
Secondary	HIV viral suppression	HIV viral suppression using different thresholds (<20 copies/mL; <100 copies/mL; <1000 copies/mL)	at 26 (22 - 40) weeks