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.: PACTR201901672543518 Date of Approval: 14/01/2019
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Enhanced screening and management for advanced HIV patients, incorporating Cryptococcal disease prevention, TB treatment and same day/rapid ART Initiation: a stepped wedge cluster randomised trial
Official scientific title Enhanced screening and management for advanced HIV patients, incorporating Cryptococcal disease prevention, TB treatment and same day/rapid ART Initiation: a stepped wedge cluster randomised trial
Brief summary describing the background and objectives of the trial The overall goal of this study is to provide evidence on the feasibility, acceptability and impact on patient retention of a package of care for individuals with advanced HIV. The package will include early diagnosis and treatment for TB, early diagnosis and treatment for cryptococcal disease, prevention of opportunistic infections, rapid ART initiation (for naïve) and enhanced patient follow up on a community level including screening for TB and Cryptococcal Immune Reconstitution Inflammatory Syndrome (IRIS). Study objectives: • To improve retention in care among HIV-positive patients with severe immunosuppression • To increase detection of both pulmonary and extra-pulmonary TB among HIV-positive patients with severe immunosuppression • To increase detection and provision of prophylactic treatment for cryptococcal antigenaemia among HIV-positive patients with severe immunosuppression • To assess the feasibility and acceptability of the overall intervention at the primary health care level
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Cryptococcal disease,HIV/AIDS,Tuberculosis
Purpose of the trial Diagnosis / Prognosis
Anticipated trial start date 02/07/2018
Actual trial start date
Anticipated date of last follow up 01/02/2021
Actual Last follow-up date
Anticipated target sample size (number of participants) 900
Actual target sample size (number of participants)
Recruitment status 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
Crossover: all participants receive all interventions in different sequence during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Enhanced package of care for TB and Cryptoccocal disease in individuals with advanced HIV 12 months Routine measurement of CD4 using PIMA at the Point of Care (POC) is used for all new patients who test HIV positive and all patients returning to care after having disengaged from care for more than 3 months. Additionally patients found to have a VL>1000 during routine follow up will have their CD4 count measured with regular laboratory testing. Those found with CD4 < 200 as determined by the PIMA CD4, or laboratory test, will be eligible for the intervention which in brief will include: 1. CD4 (Routine Point of Care CD4 (PIMA) for all new HIV positive patients (ART naïve) and all patients returning to care after defaulting (>3 months)) 2. TB Screening and Diagnosis (Symptom screening; Systematic GeneXpert; Systematic TB LAM; Systematic sputum culture; and Drug susceptibility testing) 3. TB prevention (Isoniazide Preventive Therapy systematically) 4. Cryptococcal disease (Systematic screening with POC CrAg LFA for all with CD4<200) 5. TB treatment (Standard dose Rifampicin (10mg/kg)) 6. Community follow up (Systematic home visit to detect IRIS early; and Systematic follow up for missed appointments) 7. ART initiation (Same day ART initiation (for naïve) for all patients who screen negative for TB and Cryptococcal disease) 450
Control Group South African standard of care for individuals with advanced HIV disease 12 months 1. CD4 (Laboratory CD4 testing is required for all new HIV positive patients; CD4 testing is not systematically used for patients returning to care after defaulting 2. TB Screening and Diagnosis (Symptom screening; GeneXpert if suspicion of TB; Sputum culture and DST if GXP negative; TB LAM not used ) 3. TB prevention (IPT systematically) 4. Cryptococcal disease (Screening by reflex CrAg for all with CD4 < 100) 5. TB treatment (Standard dose Rifampicin (10mg/kg)) 6. Community follow up (Systematic follow up for missed appointments) 7. ART initiation (Fast track ART initiation (for naïve) for all HIV patients* before any lab results are available (patient to return within a week for results)) 450 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1) Patients aged 18 years and older 2) New HIV positive patients with CD4< 200 cell counts/µl 3) Immunosuppressed on ART treatment patients with VL>1000 copies/ml and CD4<200 cell counts/ µl 4) Patients returning after defaulting for more than 3 months with a CD4<200 5) Written, informed consent for data collection (control and intervention arms) 6) Written, informed consent for participation in intervention (intervention arm) 1) Patients requiring hospitalization 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) 100 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
Yes 31/01/2018 University of cape Town Human Reaserch Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Room E53-46 Old Main Building, Groote Schuur Hospital, Observatory Cape Town 7925 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/03/2018 Ethics Review Board Instituted by Medecins Sans Frontieres
Ethics Committee Address
Street address City Postal code Country
368 Main Rd, fourth floor Deneb House Cape Town 3973 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Proportion of patients initiated < 200 CD4 retained in care at 6 months and 12 months. At 6 months and 12 months
Secondary Outcome Proportion of patients initiated < 200 CD4 diagnosed with extrapulmonary TB and pulmonary TB At enrollment - start of the follow-up
Secondary Outcome Proportion of patients with CD4 <200 found to have cryptococcal antigenaemia At enrollment - start of the follow-up
Secondary Outcome Median time to ART initiation (for naïve) At enrollment - start of the follow-up
Secondary Outcome Virological suppression (VL<1000) 6 and 12 months following ART initiation (for naïve) At 6 months and 12 months
Secondary Outcome TB outcomes for all those diagnosed with TB Throughout follow-up
Secondary Outcome Proportion of eligible patients initiating ART on the same day At enrollment - start of the follow-up
Secondary Outcome Disease free survival at 6 months on Fluconazole for the prevention of cryptococcal disease At 6 months
Secondary Outcome Overall mortality At 6 months and 12 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
King Dinizulu clinic Eshowe Service Area Eshowe South Africa
Eshowe gateway clinic Eshowe Service Area Eshowe South Africa
Sipilile clinic Eshowe Service Area Eshowe South Africa
Sinethemba clinic Eshowe Service Area Eshowe South Africa
Siyalulama clinic Mbongolwane Hospital Mbongolwane South Africa
Samungu clinic Mbongolwane Health Service Area Mbongolwane South Africa
Mathungela clinic Mbongolwane Health Service Area Mbongolwane South Africa
Osungulweni clinic Mbongolwane Health Service Area Mbongolwane South Africa
Ngudwini clinic Mbongolwane Health Service Area Mbongolwane South Africa
Ntumeni clinic Mbongolwane Health Service Area Mbongolwane South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Medecins Sans Frintieres Belgique 46, Rue de lArbre Benit Brussels 1050 Belgium
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Medecins Sans Frontieres OCB Rue de l arbre benit 46 Brussels 1050 Belgium Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Rosana Stewart 33 Main St, Eshowe Eshowe 3815 South Africa
Gabriella Ferlazzo 368 Main Rd, Observatory, fourth floor Deneb House Cape Town 3973 South Africa
Bernadette Gergonne 33 Main St Eshowe 3815 South Africa
Sarah Jane Steele 368 Main Rd, Observatory, fourth floor Deneb House Cape Town 3973 South Africa
Gilles Van Cutsem 368 Main Rd, Observatory, fourth floor Deneb House Cape Town 3973 South Africa
Petros Isaakidis 368 Main Rd, fourth floor Deneb House Cape Town 3973 South Africa
Landon Myer Groote Schuur Hospital, University of Cape Town, Observatory Cape Town 7925 South Africa
Emmanuel Thokozani 368 Main Rd, fourth floor Deneb House, Observatory Cape Town 3973 South Africa
Liesbet Ohler 33 Main St Eshowe 3815 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Amir Shroufi MSFOCB-Capetown-MedCo@brussels.msf.org +27214481058 368 Main Rd, Observatory
City Postal code Country Position/Affiliation
Cape Town 7937 South Africa Medical Coordinator
Role Name Email Phone Street address
Public Enquiries Jelena Pavlovic msfocb-capetown-epi@brussels.msf.org +27214481058 368 Main Rd, Observatory, fourth floor Deneb House
City Postal code Country Position/Affiliation
Cape Town 7937 South Africa Epidemiologist
Role Name Email Phone Street address
Scientific Enquiries Jelena Pavlovic msfocb-capetown-epi@brussels.msf.org +27214481058 368 Main Rd, Observatory, fourth floor Deneb House
City Postal code Country Position/Affiliation
Cape Town 7937 South Africa Epidemiologist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Results, whether positive or negative, will be shared with the district stakeholders and provincial stakeholders (Human Research Ethics Committee at UCT, MSF Ethics Review Board, SA government structures, community members, health care workers and other local stakeholders) through research sharing meetings, and transmitted to policy makers at the national (South African HIV Clinicians Society) and international (PACTR, WHO) level. Results will also be submitted for publication in a peer reviewed journal. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol Clinical report will be shared in two and a half years (July 2021). Report is planned to be ready 6 months after the last follow-up (expected in February 2021). Upon request, study protocol with analysis plan, including informed consent forms can be shared.
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