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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202101800561159 Date of Registration: 18/01/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A5300B/I2003B/PHOENIx
Official scientific title Protecting Households On Exposure to Newly Diagnosed Index Multidrug Resistant Tuberculosis Patients (PHOENIx MDR -TB)
Brief summary describing the background and objectives of the trial This is a phase III, open-label, multicenter trial with a cluster-randomized superiority design (eligible contacts in the same household [HH] are a cluster), to compare the efficacy and safety of 26 weeks of delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing confirmed or probable active TB during 96 weeks of follow-up among high-risk household contacts (HHCs) of adults with multidrug-resistant tuberculosis (MDR-TB). High-risk HHCs are those with HIV or non-HIV immunosuppression, latent TB infection, and young children below the age of 5 years The hypothesis is that treating child, adolescent, and adult household contacts (HHCs) of multidrug-resistant tuberculosis (MDR-TB) patients, including those with pre-extensively (pre-XDR) and extensively drug resistant (XDR) TB, who are at high risk of developing TB with delamanid (DLM), will substantially reduce the risk of developing TB compared with treatment with isoniazid (INH) preventive therapy. The 2 primary objectives are to 1) compare the efficacy of 26 weeks of DLM versus 26 weeks of INH for preventing confirmed or probable active TB during 96 weeks of follow and 2) To compare the safety (permanently stopping study drug due to treatment-related adverse events) of 26 weeks of DLM versus 26 weeks of INH for the treatment of presumed latent TB infection (LTBI) with MDR-TB.
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 Tuberculosis
Purpose of the trial Prevention
Anticipated trial start date 02/11/2020
Actual trial start date
Anticipated date of last follow up 30/06/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 5610
Actual target sample size (number of participants)
Recruitment status Active, not 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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Dynamic (adaptive) random allocation such as minimization Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Delamanid Adults and children ≥30 kg HHCs: Delamanid will be administered orally (four 50 mg tablets [200 mg]) once daily preferably with food with a high fat content. Children ≥2.5 kg to <30 kg HHCs: Delamanid will be administered orally once daily preferably with food with a high fat content, according to the appropriate dose 2.5 to <12kg 30mg, 12 to <20kg 50mg, 20 to <25kg 100mg and 25 to <30kg 150mg. 26 weeks Guideline recommend use of isoniazid for the prevention of TB in HIV positive contacts of MDR TB patients. This recommendation is however not based on high quality evidence. Based on recent studies, delamanid has shown promising results in treatment of MDR TB patients when combined with other antituberculous drugs. No studies have evaluated its use in the prevention of TB. This study is designed to access superiority of delamanid over isoniazid in the prevention of MDR TB. It will also involve use of electronic drug monitoring devices to access and improve adherence. 2805
Control Group Isoniazid Adults and children ≥24 kg: INH 300 mg orally once daily Children ≥2.5 kg to <24 kg: INH weight-band dosing orally once daily 2.5 to <6 kg 50mg, 6 to <10 kg 100mg, 10 to <14 kg 150mg, 14 to <20 kg 200mg, 20 to <24 kg 250mg 26 weeks Guideline recommend use of isoniazid for the prevention of TB in HIV positive contacts of MDR TB patients. Therefore the study will utilise this standard of care as the control arm to compare it to delamanid. 2805 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
INDEX CASE Confirmed Pulmonary MDR-TB Men and women age ≥18 years HOUSEHOLD CONTACTS Children 0 to <5 years of age HIV+ or non-HIV immunosuppressed adults and children ≥5 years of age TST+ and/or IGRA+ adults and children ≥5 years of age not HIV+ or non-HIV immunosuppressed For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to study entry For infants (0 to 1 year of age), weight ≥2.5 kg at screening Chest radiograph without evidence of active TB performed within 70 days prior to study entry for HHCs ≥2 years of age and within 30 days prior to study entry for HHCs <2 years of age. QTcF interval ≤460 ms within 30 days prior to study entry as confirmed by the central ECG reading center Enrollment of the HHC within 30 days after the index case is enrolled. INDEX CASE Has previously enrolled into the A5300B/I2003B/PHOENIx trial as an index case or HHC, or is a member of a HH which has previously enrolled into the A5300B/I2003B/PHOENIx trial. HOUSEHOLD CONTACT Current confirmed or probable or possible pulmonary or extrapulmonary TB, Receipt of more than 30 cumulative days of INH, rifamycin, fluoroquinolone, or DLM in the 90 days prior to study entry. History of or current liver cirrhosis at any time prior to study entry Evidence of acute hepatitis, such as abdominal pain, nausea and vomiting, jaundice, dark urine, and/or light stools within 90 days prior to study entry Peripheral neuropathy ≥Grade 2 within 90 days prior to study entry Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation Current cardiovascular disorder that is clinically relevant in the opinion of the site investigator Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements Serious illness requiring systemic treatment including parenteral therapy (e.g., antibiotics) and/or hospitalization within 30 days prior to study entry. Currently receiving other medication with potential for adverse drug-drug interactions, including QT prolongation. Taken an investigational drug or vaccine within 30 days prior to study entry. Has a clinical condition that in the site investigator’s opinion would interfere with study participation. Has enrolled into a TB vaccine or TB preventive therapy or TB therapeutic trial, including the A5300B/I2003B/PHOENIx trial in the two years prior to study entry. Not expected to be able to complete 96 weeks of study follow-up 80 and over: 80+ Year,Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Child: 6 Year-12 Year,Infant: 1 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),New born: 0 Day-1 Month,Preschool Child: 2 Year-5 Year 0 Year(s) 80 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 31/01/2019 Moi University Moi Teaching and Referral Hospital Institutional Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Moi Teaching and Referral Hospital. Nandi road Eldoret 3 - 30100 Kenya
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 30/09/2019 Pharmacy and Poisons Board
Ethics Committee Address
Street address City Postal code Country
Lenana Road Eldoret 27663 Kenya
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 31/01/2019 Moi University and Moi Teaching and Referral Hospital Institutional Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Moi Teaching and Referral Hospital - Nandi Road Eldoret 30100 Kenya
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 08/10/2019 Pharmacy and Poisons Board
Ethics Committee Address
Street address City Postal code Country
Lenana Road Nairobi 27663 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Efficacy The primary outcome measure is the occurrence of confirmed or probable active TB at any time between Day 0 and the week 96 study visit . This will be evaluated at the individual participant level. An independent outcomes review committee will review diagnoses of active TB made by the participating sites and deaths. This committee will include clinicians who are experts in the diagnosis of TB in adults, adolescents, and children. The committee will not include members who are directly involved with the care of study participants or who are study team members providing participant management guidance to site investigators. The committee will be blinded to treatment assignment. Only confirmed and probable active TB cases that are validated by the independent outcomes review committee will be included in the primary efficacy analysis. The independent outcomes review committee will also determine the date that a HHC first met the criteria for confirmed or probable active TB. Safety The primary safety outcome measure is the permanent discontinuation of randomized study drug (DLM or INH) due to a treatment-related adverse event (i.e., requiring discontinuation, or in the opinion of the site investigator is a treatment-limiting adverse event). This will be evaluated at the individual participant level. Day 0 and the week 96 study visit
Secondary Outcome Efficacy - Death from any cause at any time between Day 0 and 96 weeks of follow-up, or the occurrence of confirmed or probable active TB or confirmed active MDR-TB at any time between Day 0 and the week 96 study visit. Safety - Occurrence of a Grade 3 or higher adverse event during the period receiving randomized study drug (DLM or INH). If a HHC has a Grade 3 or 4 event prior to starting randomized study drug, then the same event will only be considered during follow-up if the grade worsens. Between Day 0 and 96 weeks
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Moi University Clinical Research Centre Chandaria Cancer and Chronic Diseases Centre, at MTRH Second Floor. Nandi Road Eldoret 4606 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development 5601 Fishers Lane, MSC 9806 Bethesda, MD 20892-9806 Maryland United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development 5601 Fishers Lane, MSC 9806 Bethesda, MD 20892-9806 Maryland United States of America Government Body
COLLABORATORS
Name Street address City Postal code Country
Gavin Churchyard Postnet Suite 300, Private Bag X30500, Houghton, 2041 SOUTH AFRICA Hougton 2041 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Gavin Churchyard gchurchyard@auruminstitute.org +27105901306 The Aurum Institute Aurum House, The Ridge, 29 Queens Road Parktown, Johannesburg, 2193 Postnet Suite 300, Private Bag X30500, Houghton,
City Postal code Country Position/Affiliation
Johannesburg South Africa Protocol Chairperson
Role Name Email Phone Street address
Public Enquiries Lara Hosey lara.hosey@dlhcorp.com 3016283395 8757 Georgia Avenue, 12th Floor Silver Spring, MD
City Postal code Country Position/Affiliation
Maryland United States of America Clinical Trials Specialist
Role Name Email Phone Street address
Scientific Enquiries Tafadzwa Kasambira tafadzwa.kasambira@nih.gov 2406273857 5601 Fishers Lane, 8B27 Rockville, MD
City Postal code Country Position/Affiliation
Maryland United States of America Clinical Representative
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Efforts are made to keep participants' personal information confidential. They will each be assigned a personal Identification number. These PIDs are what will be used to identify the participants. However this information may be disclosed if required by law. Informed Consent Form,Statistical Analysis Plan,Study Protocol The study protocol, statistical analysis plan and unsigned Informed consent forms are available at the beginning of the study and can be availed to any relevant authorities. The final study report will only be available once the study close out has taken place and all data analysis has been done. Records may be reviewed by the ACTG, IMPAACT, United States (US) Office for Human Research Protections (OHRP), the Kenya Ministry of Health, the Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee, the United States Army Medical Research and Development Command (USAMRDC), National Institutes of Health (NIH), other government agencies, study staff, study monitors, and drug companies supporting this study and their designees.
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