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.: PACTR201402000765312 Date of Approval: 06/02/2014
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title ISAAC 004
Official scientific title Effect of an Intensified Patient-specific TB Diagnostic Strategy on Treatment Decisions by Physicians Caring for Adults and Children with Suspected Pulmonary Tuberculosis in the Kilimanjaro Region of Tanzania
Brief summary describing the background and objectives of the trial While availability of culture is assumed to improve management of tuberculosis in resource-limited settings, the degree to which availability of tuberculosis culture results change management decisions and clinical outcomes in a setting where clinical diagnosis is the norm has never been documented systematically. Early death, loss to follow up after initial sputum testing, and clinicians¿ reluctance to exclude a diagnosis of tuberculosis even with a negative culture all may lessen the impact of tuberculosis culture results. This study sought to determine the impact of culture-driven diagnostics versus standard of care (un-concentrated sputum smear) on physician treatment decisions for patients with suspected pulmonary tuberculosis.
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 Diagnosis / Prognosis
Anticipated trial start date 18/11/2008
Actual trial start date 18/11/2008
Anticipated date of last follow up 14/09/2009
Actual Last follow-up date 14/09/2009
Anticipated target sample size (number of participants) 120
Actual target sample size (number of participants) 70
Recruitment status Completed
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
Parallel: different groups receive different interventions at same time during study Randomised stratified by age less than 6 years or greater than or equal to 6 years; for each age group used simple randomization using a computer-based program randomization.com randomization assignments were pre-prepared by an individual not participating in the conduct of the trial and placed in ordered, sealed envelopes at the site of randomization Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised stratified by age less than 6 years or greater than or equal to 6 years; for each age group used simple randomization using a computer-based program randomization.com randomization assignments were pre-prepared by an individual not participating in the conduct of the trial and placed in ordered, sealed envelopes at the site of randomization Open-label(Masking Not Used)
Parallel: different groups receive different interventions at same time during study Randomised stratified by age less than 6 years or greater than or equal to 6 years; for each age group used simple randomization using a computer-based program randomization.com randomization assignments were pre-prepared by an individual not participating in the conduct of the trial and placed in ordered, sealed envelopes at the site of randomization Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Standard diagnostics 3 sputum or gastric aspriate specimens for standard unconcentrated smear for acid fast bacilli 3 days standard of care for tuberculosis diagnosis 37 Active-Treatment of Control Group
Experimental Group Intensified diagnostics 3 sputum or gastric aspriate specimens for concentrated smear for acid fast bacilli and liquid culture for tuberculosis 3 days addition of culture and concentrated smear to standard smear-only diagnostics 33
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
For all participants: Are able and willing to provide written informed consent if aged 18 or older, assent if aged 12-17, or legal guardian able to consent if <12 years of age. Reside within the Kilimanjaro Region of Tanzania. Are willing to be tested for HIV-1. For adults and children > or equal to 6 years of age- Are suspected to have pulmonary tuberculosis, defined as: Cough for 2 or more weeks and one or more of the following, without another substantiated diagnosis (e.g., cytology showing lung cancer) Reported or documented recurrent fever, ¿38.0 C, over previous 2 weeks Weight loss or failure to thrive not explained through poor nutrition Night sweats recurrent over previous 2 weeks Hemoptysis CXR consistent with TB OR Physician suspicion of pulmonary tuberculosis For children <6 years of age: Are suspected to have pulmonary tuberculosis, defined as: Any 2 of the following symptoms, without another substantiated diagnosis Cough or shortness of breath for 2 or more weeks Reported or documented recurrent fever, ¿38.0 C, over previous 2 weeks Weight loss or failure to thrive not explained through poor nutrition Night sweats recurrent over previous 2 weeks Exposure to adult with pulmonary TB in last 2 years CXR consistent with TB OR Physician suspicion of pulmonary tuberculosis AND are willing to undergo gastric aspirate Have received more than 3 days of anti-TB therapy in the 2 weeks preceding enrollment, or more than 2 weeks of anti-TB treatment in the 3 months preceding enrollment. This includes prophylactic INH in an exposed child or adult. Have been previously included in the ISAAC 004 protocol Participating in another research study that in the opinion of the PI would influence the likelihood of TB treatment completion or other ISAAC 004 study aims or exceed the maximum blood volume for laboratory testing. Have an obvious psychological or psychiatric disorder that would preclude provision of informed consent or otherwise contraindicate study participation, or for children < 18 years, the only available legal guardian has such a condition. Have been conclusively or presumptively diagnosed with another condition explaining the symptoms and the possibility of TB is not under active consideration by the clinical care providers Subjects who undergo bronchoscopy to obtain BAL will be ineligible for the study 0 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 27/12/2007 Kilimanjaro Christian Medical Centre Ethics Committee
Ethics Committee Address
Street address City Postal code Country
KCMC Hospital Sokoine Rd. Box 3010 Moshi n/a Tanzania
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 08/02/2008 National Institute for Medical Research Tanzania
Ethics Committee Address
Street address City Postal code Country
2448 Ocean Rd. Box 9653 Dar es Salaam n/a Tanzania
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 07/02/2008 Duke University Health Center Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
2424 Erwin Rd. Durham 27705 United States of America
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Initiation of anti-tuberculosis medication by tuberculosis status as determined by microbiologic and clinical assessment committee diagnosis 4 weeks after enrollment 8 weeks after enrollment at time of death or loss to follow up, if possible to ascertain
Secondary Outcome Initiation of anti-tuberculosis medication among smear-negative participants according to randomization arm 4 weeks 8 weeks death or loss to follow up
Secondary Outcome Initiation of anti-tuberculosis medication by HIV infection status and randomization arm 4 weeks 8 weeks death or loss to follow up
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kilimanjaro Christian Medical Centre Sokoine Road Box 3010 Moshi n/a Tanzania
Mawenzi Regional Hospital Kilima Road Moshi n/a Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
U.S. National Institutes of Health 9000 Rockville Pike Bethesda 20892 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor U.S. National Institutes of Health 9000 Rockville Pike Bethesda 20892 United States of America Funding Agency
Secondary Sponsor Kilimanjaro Christian Medical Centre Sokoine Rd. Box 3010 Moshi n/a Tanzania Hospital
Secondary Sponsor Duke University Medical Center Division of Infectious Disease Hanes House Trent Dr. Box 102359 Durham 27710 United States of America University
COLLABORATORS
Name Street address City Postal code Country
Carol Hamilton 359 Blackwell St. Suite 200 Durham 27701 United States of America
Elizabeth Reddy KCMC Hospital Sokoine Rd. Box 3010 Moshi n/a Tanzania
Susan Morpeth KEMRI Wellcome Trust Research Programme PO Box 230 Kilifi 80108 Kenya
Boniface Njau KCMC Hospital Sokoine Rd. Box 3010 Moshi n/a Tanzania
Venance Maro KCMC Hospital Sokoine Rd. Box 3010 Moshi n/a Tanzania
Levina Msuya KCMC Hospital Sokoine Rd. Box 3010 Moshi n/a Tanzania
Annie Morrissey Hanes House Trent Dr. Box 102359 Durham 27710 United States of America
Coleen Cunninham Duke University Department of Pediatrics T901 Children's Health Center Durham 27710 United States of America
Kathryn Lancaster University of North Carolina School of Public Health 421 Pittsboro St. Chapel Hill 27599 United States of America
Gibson Kibiki KCMC Hospital Sokoine Rd. Box 3010 Moshi n/a Tanzania
Jason Stout Hanes House Trent Dr. Box 102359 Durham 27710 United States of America
John Crump University of Otago 364 Laith Walk Dunedin 9016 New Zealand
John Bartlett Duke Global Health Institute Trent Dr. Durham 27710 United States of America
John Shao KCMC Hospital Sokoine Rd. Box 3010 Moshi n/a Tanzania
Coleen Cunningham Duke University Department of Pediatrics T901 Children's Health Center Durham 27710 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Carol Hamilton chamilton@fhi360.org 919-405-1444 359 Blackwell St. Suite 200
City Postal code Country Position/Affiliation
Durham 27701 United States of America Director, Scientific Affairs, Global Health, Population & Nutrition
Role Name Email Phone Street address
Public Enquiries Elizabeth Reddy elizabeth.reddy@duke.edu 255 272754086 KCMC Hospital Box 3010
City Postal code Country Position/Affiliation
Moshi n/a Tanzania Assistant Professor of Medicine, Duke University Division of Infectious Disease
Role Name Email Phone Street address
Scientific Enquiries Carol Hamilton chamilton@fhi360.org 919-405-1444 359 Blackwell St. Suite 200
City Postal code Country Position/Affiliation
Durham 27701 United States of America Director, Scientific Affairs, Global Health, Population & Nutrition
REPORTING
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URL Results Available Results Summary Result Posting Date First Journal Publication Date
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information