HIV InfectionPhase 4PrOMPTNCT01417988
Prevention of Early Mortality by Presumptive Tuberculosis (TB) Treatment
A Phase 4 study testing Experimental: Empiric TB treatment and ART only arm in people with HIV Infection and Tuberculosis, run by Prof JMA Lange at 3 sites in 3 countries.
Trial summary
This study investigates the prevention of early mortality in patients initiating antiretroviral therapy (ART) in sub-Saharan Africa where 79% of the co-infected cases of TB reside. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection, Tuberculosis
- What is being tested?
- Experimental: Empiric TB treatment and ART only arm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Aug 2011to Jun 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged > 18 years old
- HIV-1 positive
- Eligible for antiretroviral treatment with CD4 T cell count < 50 cells/μl
- BMI < 18
Who cannot join
- Patients with smear-positive pulmonary TB
- Patients who fulfill the diagnostic criteria for smear-negative pulmonary or extrapulmonary TB (http://www.who.int/tb/publications/2006/tbhiv_recommendations.pdf ).
- Previous TB treatment (history of TB medication for > 1 month
- History of using antiretroviral drugs
- Symptomatic known underlying liver disease or transaminases > 5x upper limit of normal
- Known or suspected drug resistance to more than one first-line TB drug according to WHO criteria but excluding HIV infection (e.g. household contacts of MDRTB patients)
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- Pregnant or breast-feeding
- Patients with cryptococcal meningitis (CrAG positive with neurologic symptoms)
- Patients with other severe (opportunistic) disease such as disseminated KS, malignant lymphoma, toxoplasmosis who may not be able to tolerate anti-TB medication or require other specific therapy
- Patients with danger signs (respiratory rate > 30 per minute, heart rate > 120bpm, temperature > 39oC, and unable to ambulate)
- Taking other potentially life-saving medications (e.g. for other OIs, or immunosuppressants) that are incompatible with anti-TB chemotherapy or ART
- Unable to swallow TB medications
- Unable to follow-up at the clinic for regularly scheduled follow-up (e.g. too far from clinic)
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Mozambique1 site
Ministry of Health -Provincial Heatlh Directorate of the Sofala Province (Direcção Provincial de Saúde de Sofala DPSS)
Beira
About this study
Official title: Prevention of Early Mortality by Presumptive TB Treatment in HIV-infected Patients Initiating Antiretroviral Therapy
This study investigates the prevention of early mortality in patients initiating antiretroviral therapy (ART) in sub-Saharan Africa where 79% of the co-infected cases of TB reside. Many published studies have shown a surprisingly high proportion of all patients initiated on ART dying within 6 months (8-26%) with increasing risk with decreasing CD4 T cell count. The majority (median 70%) occur in the first 3 months with the greatest proportion of deaths due to previously undiagnosed tuberculosis (TB). The investigators will enroll patients from 4 geographically diverse countries (Gabon, Mozambique, South Africa, and Uganda) in a randomized open label clinical trial targeting a population of people with high mortality risk; patients with CD4 T cell count < 50 cells/μl and body mass index (BMI) < 18 kg/m2. Severely immunocompromised patients with low BMI in the intervention arm will receive presumptive anti-TB 4-drug chemotherapy and subsequently initiate ART within 2 weeks compared to ART alone. The main objective is to measure and compare early mortality in the group presumptively treated for TB in addition to ART. Other sub-objectives are to determine the predictors of early mortality and the causes of death by autopsy (traditional and verbal), to determine if presumptive anti-TB treatment affects viral suppression with ART, and to assess incidence rates and characterize drug toxicity in patients dually treated. Because of the high rates of TB co-infection in sub-Saharan Africa in the HIV-infected, the investigators expect that patients presumptively treated for TB in addition to HIV will have a lower mortality rate than patients receiving ART only. This trial is expected to be of great public health benefit and generalisability.
- Conditions
- HIV Infection, Tuberculosis
- Being tested
- Experimental: Empiric TB treatment, ART only arm
- Keywords
- TB
- Medical subject headings
- HIV Infections, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental: Empiric TB treatmentDrug
Initiation of 4 drug TB treatment (8 weeks of 4 drug, 16 weeks of 2 drug therapy) followed by ART (efavirenz-based) within 2 weeks
ART only armDrug
ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment
| Study group | Role | What they receive |
|---|---|---|
| Empiric TB treatment | Experimental | Empiric initiation of 4 drug TB treatment (8 weeks of 4 drug, 16 weeks of 2 drug therapy) followed by ART (efavirenz-based) within 2 weeks Receives: Drug: Experimental: Empiric TB treatment |
| ART only arm | Active comparator | ART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment Receives: Drug: ART only arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality in the first 24 weeks after initiation of ART
Measured: 24 weeks
Secondary outcomes (5)
CD4 T cell absolute increase
Measured: 24 weeks
Causes of death
Measured: 24 weeks
Safety and tolerability of anti-tuberculous medications
Measured: 24 weeks
HIV viral suppression
Measured: 24 weeks
TB incidence rates after ART initiation
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionJun 2013
- Study completionJun 2013
Why it stopped: Study was terminated prematurely due to insufficient enrolment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof JMA Lange
- Sponsor type
- University, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor-investigator, Prof JMA Lange, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Frank Cobelens, Study director, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)Yuka Manabe, Principal investigator, Infectious Diseases Institute at Makerere University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01417988
- Sponsor's protocol ID
- AIGHD_001
- Acronym
- PrOMPT
- Status last verified
- Feb 2014
- First submitted
- 25 Jul 2011
- Last updated
- 17 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Early Mortality by Presumptive TB Treatment in HIV-infected Patients Initiating Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT01417988
- Acronym / sponsor ID
- PrOMPT / AIGHD_001
- Conditions
- HIV Infection, Tuberculosis
- Keywords
- TB
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated prematurely due to insufficient enrolment.
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Prof JMA LangeUniversity, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- Aug 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 16 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study investigates the prevention of early mortality in patients initiating antiretroviral therapy (ART) in sub-Saharan Africa where 79% of the co-infected cases of TB reside. Many published studies have shown a surprisingly high proportion of all patients initiated on ART dying within 6 months (8-26%) with increasing risk with decreasing CD4 T cell count. The majority (median 70%) occur in the first 3 months with the greatest proportion of deaths due to previously undiagnosed tuberculosis (TB). The investigators will enroll patients from 4 geographically diverse countries (Gabon, Mozambique, South Africa, and Uganda) in a randomized open label clinical trial targeting a population of people with high mortality risk; patients with CD4 T cell count < 50 cells/μl and body mass index (BMI) < 18 kg/m2. Severely immunocompromised patients with low BMI in the intervention arm will receive presumptive anti-TB 4-drug chemotherapy and subsequently initiate ART within 2 weeks compared to ART alone. The main objective is to measure and compare early mortality in the group presumptively treated for TB in addition to ART. Other sub-objectives are to determine the predictors of early mortality and the causes of death by autopsy (traditional and verbal), to determine if presumptive anti-TB treatment affects viral suppression with ART, and to assess incidence rates and characterize drug toxicity in patients dually treated. Because of the high rates of TB co-infection in sub-Saharan Africa in the HIV-infected, the investigators expect that patients presumptively treated for TB in addition to HIV will have a lower mortality rate than patients receiving ART only. This trial is expected to be of great public health benefit and generalisability.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empiric TB treatment | Experimental | Drug: Experimental: Empiric TB treatmentEmpiric initiation of 4 drug TB treatment (8 weeks of 4 drug, 16 weeks of 2 drug therapy) followed by ART (efavirenz-based) within 2 weeks |
| ART only arm | Active comparator | Drug: ART only armART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Aged > 18 years old
- HIV-1 positive
- Eligible for antiretroviral treatment with CD4 T cell count < 50 cells/μl
- BMI < 18
Key exclusion criteria (13 listed)
- Patients with smear-positive pulmonary TB
- Patients who fulfill the diagnostic criteria for smear-negative pulmonary or extrapulmonary TB (http://www.who.int/tb/publications/2006/tbhiv_recommendations.pdf ).
- Previous TB treatment (history of TB medication for > 1 month
- History of using antiretroviral drugs
- Symptomatic known underlying liver disease or transaminases > 5x upper limit of normal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental: Empiric TB treatmentInitiation of 4 drug TB treatment (8 weeks of 4 drug, 16 weeks of 2 drug therapy) followed by ART (efavirenz-based) within 2 weeks | Drug | Empiric TB treatment |
| ART only armART (efavirenz-based) only (+ pyridoxine 50mg) given within 2 weeks after enrolment | Drug | ART only arm |
Primary outcome
All-cause mortality in the first 24 weeks after initiation of ART
Time frame: 24 weeks
5 secondary outcomes
CD4 T cell absolute increase
Time frame: 24 weeks
Causes of death
Time frame: 24 weeks
Safety and tolerability of anti-tuberculous medications
Time frame: 24 weeks
HIV viral suppression
Time frame: 24 weeks
TB incidence rates after ART initiation
Time frame: 24 weeks
Results and safety
The study was stopped early (reason given: Study was terminated prematurely due to insufficient enrolment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2014.
- Official Website of the sponsorLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Cobelens study director
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Yuka Manabe principal investigator
Infectious Diseases Institute at Makerere University
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Experimental: Empiric TB treatment and ART only arm in people with HIV Infection and Tuberculosis, run by Prof JMA Lange at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Gabon, Mozambique, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study was terminated prematurely due to insufficient enrolment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause mortality in the first 24 weeks after initiation of ART (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2014.