AIDS-Related Opportunistic InfectionsDREAMMNCT03226379
Driving Reduced AIDS-associated Meningo-encephalitis Mortality
A study testing DREAMM in people with AIDS-Related Opportunistic Infections and Meningo-encephalitis, run by St George's, University of London at 5 sites in 3 countries.
Trial summary
The DREAMM project is investigating whether the DREAMM interventions (1) Health system strengthening, 2) Co-designed education programs tailored to frontline healthcare workers, 3) Implementation of a diagnostic and treatment algorithm and, 4) Communities of practice in infectious diseases and laboratory capacity… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AIDS-Related Opportunistic Infections, Meningo-encephalitis, Cryptococcal Meningitis
- What is being tested?
- DREAMM
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 495 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 23 Apr 2016to Sep 2021
- Phase
- Interventional
- 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
- Consecutive patients > 18 years with 1st episode of suspected meningo- encephalitis
- Known to be HIV positive or willing to undertake an HIV test
- Willing to agree to participate in the study
Who cannot join
- Patients presenting with suspected relapse of HIV-associated meningo-encephalitis
- HIV negative patients
- Pregnant or lactating patients
- Patients presenting with a known diagnosis of primary CNS Lymphoma or cerebral malaria
- COVID-19 infected patients
- Patients who are HIV negative or are diagnosed with cerebral malaria on hospital admission or after initial investigation will be excluded or withdrawn from the DREAMM study.
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Tanzania2 sites
Amana Hospital
Dar es Salaam
Mwananyamala Hospital
Dar es Salaam
About this study
Official title: Integrating the Diagnosis and Management of HIV-associated Central Nervous System (CNS) Infections Into Routine Health Services in Low and Middle Income Countries (LMICs)
The DREAMM project is investigating whether the DREAMM interventions (1) Health system strengthening, 2) Co-designed education programs tailored to frontline healthcare workers, 3) Implementation of a diagnostic and treatment algorithm and, 4) Communities of practice in infectious diseases and laboratory capacity building) when combined reduce two week all-cause mortality of HIV-associated meningo-encephalitis in African LMICs.
Read the detailed description
HIV-associated central nervous system (CNS) infection causes significant mortality and places a high burden on limited health care resources in Sub-Saharan Africa (SSA). Cohort and autopsy studies estimate that CNS infections cause up to a third of HIV-related deaths in African LMICs.
Cryptococcal meningitis alone is estimated to account for up to 20% of HIV-related mortality and its' incidence in Africa, unlike in resource-rich settings, has remained high despite antiretroviral roll out.
In African low and middle-income countries (LMICs) mortality associated with cryptococcal meningitis has been estimated at 70% at 3 months.
Tuberculous meningitis mortality also remains unacceptably high and is reported at over 70% in a study from Cameroon. Delays in diagnosis are key causes of poor patient outcomes for tuberculous and bacterial meningitis, and cryptococcal meningitis where patients present late and with advanced disease.
The aim of the DREAMM study is to drive down this unacceptably high mortality associated with HIV-associated meningo-encephalitis in LMICs.
A further aim is to provide capacity building in implementation research at each of the sites driven by the local African Principal Investigators (PIs) (Dr Cecilia Kanyama, Lilongwe, Malawi; Dr Charles Kouanfack, Yaoundé, Cameroon; Dr Sayoki Mfinanga, NIMR, Dar es Salaam Tanzania, Dr Saulos Nyirenda, Zomba, Malawi).
The project is in three phases:
- Observation: Local clinical and laboratory procedures and practices and availability of essential drugs and diagnostic tests for routine care of HIV-associated meningo-encephalitis patients in three study countries will be observed and documented. 75 patients in total will be recruited into the observation phase of DREAMM, 25 patients from each study country.
- Training: A co-designed laboratory and clinical training program on HIV-associated meningitis in LMICs tailored to frontline healthcare workers (HCWs) will be delivered. Key clinical and laboratory routine HCWs will be trained including on the latest point of care (POC) diagnostic tests and safe administration of essential medicines for HIV-associated meningo-encephalitis such as amphotericin B deoxycholate using a Train the Trainer approach. The knowledge and skills will be disseminated widely following this training by frontline HCWs. Locally adapted optimal clinical and laboratory pathways for the diagnosis and treatment of HIV-related meningoencephalitis in resource limited settings will be devised during the training phase using a health system engineering approach.
- Implementation: Implementation of an algorithmic approach to diagnosis and treatment of HIV-associated meningitis including aggressive microbiological detection and treatment of cryptococcosis and tuberculosis in the five study sites. The aim is to reduce the time from participant presentation to diagnostic testing and administration of effective, microbiologically-driven treatment. As part of the implementation of the algorithm, the optimised clinical and laboratory pathways endorsed by local leadership are implemented. Communities of practice are formed with weekly multidisciplinary meetings to discuss clinical cases and continue laboratory capacity building.
The data from the observation and implementation phases of the study will be fed back to local ministries of health (MOH), and access to essential antifungal drugs and diagnostic tests for HIV-associated meningitis improved and finally, cohesive HIV-related meningitis guidelines for African LMICs developed.
Important sub-studies include a health economics evaluation study to determine the cost of the intervention and routine care costs. A new semi-quantitative cryptococcal antigen lateral flow assay (CrAg LFA) (CryptoPS, Biosynex, Strasburg, France) will be evaluated uniquely for the diagnosis of patients with meningo-encephalitis. New, POC polyvalent tests (CrAg/HIV) and (CrAg/Streptococcus pneumoniae) will also be evaluated.
These POC tests nested within algorithms, and the new tests being evaluated, together with administration of recommended, microbiologically driven treatments have the potential to significantly reduce CNS infection-related mortality by reducing delays in proven diagnosis and initiation of effective treatments.
- Conditions
- AIDS-Related Opportunistic Infections, Meningo-encephalitis, Cryptococcal Meningitis, Bacterial Meningitis, Tuberculous Meningitis, Cerebral Toxoplasmosis
- Being tested
- DREAMM
- Keywords
- HIV related Meningitis, AIDS-Related Opportunistic Infections, Advanced HIV Disease, Health Systems Strengthening, Education Programmes
- Medical subject headings
- AIDS-Related Opportunistic Infections, Meningitis, Cryptococcal, Meningitis, Bacterial, Tuberculosis, Meningeal, Toxoplasmosis, Cerebral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DREAMMOther
4 DREAMM interventions to reduce HIV-related meningoencephalitis mortality once access to essential diagnostic tests and medicines:
- Health system strengthening
- Delivery of a co-designed education program tailored to frontline healthcare workers
- Implementation of an algorithm for HIV-related meningoencephalitis
- Infectious diseases/AHD mentorship and laboratory capacity building
| Study group | Role | What they receive |
|---|---|---|
| DREAMM | Other | 4 DREAMM interventions to reduce HIV-related meningoencephalitis mortality once access to essential diagnostic tests and medicines:
1. Health system strengthening
2. Delivery of a co-designed education program tailored to frontline healthcare workers
3. Implementation of an algorithm for HIV-related meningoencephalitis
4. Infectious diseases/AHD mentorship and laboratory capacity building Receives: Other: DREAMM |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-week all-cause mortality
2-week all-cause mortality from enrolment
Measured: 2 weeks from enrolment
Secondary outcomes (8)
10-week all-cause mortality
10-week all-cause mortality from enrolment
Measured: 10 weeks from enrolment
4-week all-cause mortality
4-week all-cause mortality 4 weeks from enrolment
Measured: 4 weeks from enrolment
10-week and 6-month rate of death
10-week and 6-month rate of death 10 weeks and 6 months from enrolment
Measured: 10 weeks and 6 months from enrolment
Time to appropriate investigation: lumbar puncture, brain imaging
Time to appropriate investigation: lumbar puncture, brain imaging 10 weeks from enrolment
Measured: 10 weeks from enrolment
Time to appropriate, microbiologically guided treatment
Time to appropriate, microbiologically guided treatment 10 weeks from enrolment
Measured: 10 weeks from enrolment
Prevalence of cryptococcal, tuberculous and bacterial meningitis and toxoplasma meningo-encephalitis and neurosyphilis
Prevalence of cryptococcal, tuberculous and bacterial meningitis and toxoplasma 10 weeks from enrolment
Measured: 10 weeks from enrolment
Time to ART initiation
Time to ART initiation 10 weeks from enrolment
Measured: 10 weeks from enrolment
6-month all-cause mortality
6-month all-cause mortality 6 months from enrolment
Measured: 6 months from enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start23 Apr 2016
- Primary completionApr 2021
- Study completionSep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AIDS-Related Opportunistic InfectionsStudies 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 N/A
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Cohort study with a before and after design
- Masking
- None (open label)
- Enrolment
- 495 participants (actual)
Sponsor and investigators
- Lead sponsor
- St George's, University of London
- Sponsor type
- University, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP), National Agency for Research on AIDS and Viral Hepatitis (ANRS), Institut Pasteur, National Institute for Medical Research, Tanzania, Amana Hospital, Dar es Salaam, Tanzania, University of North Carolina Project-Malawi (UNC Project), Lilongwe, Malawi, Kamuzu Central Hospital, Yaounde Central Hospital, Zomba Central Hospital, Zomba, Malawi, Lighthouse Trust, Mwananyamala Hospital, Dar es Salaam, Tanzania
- Responsible party
- Sponsor
- Investigators
- Angela Loyse, MD, Principal investigator, St George's, University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03226379
- Sponsor's protocol ID
- 16.0091
- Acronym
- DREAMM
- Status last verified
- Apr 2022
- First submitted
- 31 May 2017
- Last updated
- 4 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Mfinanga S, Kanyama C, Kouanfack C, Nyirenda S, Kivuyo SL, Boyer-Chammard T, Phiri S, Ngoma J, Shimwela M, Nkungu D, Fomete LN, Simbauranga R, Chawinga C, Ngakam N, Heller T, Lontsi SS, Aghakishiyeva E, Jalava K, Fuller S, Reid AM, Rajasingham R, Lawrence DS, Hosseinipour MC, Beaumont E, Bradley J, Jaffar S, Lortholary O, Harrison T, Molloy SF, Sturny-Leclere A, Loyse A; DREAMM Consortium. Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study. Lancet HIV. 2023 Oct;10(10):e663-e673. doi: 10.1016/S2352-3018(23)00182-0.
PubMed 37802567
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Integrating the Diagnosis and Management of HIV-associated Central Nervous System (CNS) Infections Into Routine Health Services in Low and Middle Income Countries (LMICs)
- ClinicalTrials.gov ID
- NCT03226379
- Acronym / sponsor ID
- DREAMM / 16.0091
- Conditions
- AIDS-Related Opportunistic Infections, Meningo-encephalitis, Cryptococcal Meningitis, Bacterial Meningitis, Tuberculous Meningitis, Cerebral Toxoplasmosis
- Keywords
- HIV related Meningitis, AIDS-Related Opportunistic Infections, Advanced HIV Disease, Health Systems Strengthening, Education Programmes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 495 participants (actual)
- Lead sponsor
- St George's, University of LondonUniversity, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP), National Agency for Research on AIDS and Viral Hepatitis (ANRS), Institut Pasteur, National Institute for Medical Research, Tanzania, Amana Hospital, Dar es Salaam, Tanzania, University of North Carolina Project-Malawi (UNC Project), Lilongwe, Malawi, Kamuzu Central Hospital, Yaounde Central Hospital, Zomba Central Hospital, Zomba, Malawi, Lighthouse Trust, Mwananyamala Hospital, Dar es Salaam, Tanzania
- Study start
- 23 Apr 2016 (actual)
- Primary completion
- Apr 2021 (actual)
- Study completion
- Sep 2021 (actual)
- First posted
- 21 Jul 2017 (actual)
- 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.
The DREAMM project is investigating whether the DREAMM interventions (1) Health system strengthening, 2) Co-designed education programs tailored to frontline healthcare workers, 3) Implementation of a diagnostic and treatment algorithm and, 4) Communities of practice in infectious diseases and laboratory capacity building) when combined reduce two week all-cause mortality of HIV-associated meningo-encephalitis in African LMICs.
Detailed description
HIV-associated central nervous system (CNS) infection causes significant mortality and places a high burden on limited health care resources in Sub-Saharan Africa (SSA). Cohort and autopsy studies estimate that CNS infections cause up to a third of HIV-related deaths in African LMICs.
Cryptococcal meningitis alone is estimated to account for up to 20% of HIV-related mortality and its' incidence in Africa, unlike in resource-rich settings, has remained high despite antiretroviral roll out.
In African low and middle-income countries (LMICs) mortality associated with cryptococcal meningitis has been estimated at 70% at 3 months.
Tuberculous meningitis mortality also remains unacceptably high and is reported at over 70% in a study from Cameroon. Delays in diagnosis are key causes of poor patient outcomes for tuberculous and bacterial meningitis, and cryptococcal meningitis where patients present late and with advanced disease.
The aim of the DREAMM study is to drive down this unacceptably high mortality associated with HIV-associated meningo-encephalitis in LMICs.
A further aim is to provide capacity building in implementation research at each of the sites driven by the local African Principal Investigators (PIs) (Dr Cecilia Kanyama, Lilongwe, Malawi; Dr Charles Kouanfack, Yaoundé, Cameroon; Dr Sayoki Mfinanga, NIMR, Dar es Salaam Tanzania, Dr Saulos Nyirenda, Zomba, Malawi).
The project is in three phases:
- Observation: Local clinical and laboratory procedures and practices and availability of essential drugs and diagnostic tests for routine care of HIV-associated meningo-encephalitis patients in three study countries will be observed and documented. 75 patients in total will be recruited into the observation phase of DREAMM, 25 patients from each study country.
- Training: A co-designed laboratory and clinical training program on HIV-associated meningitis in LMICs tailored to frontline healthcare workers (HCWs) will be delivered. Key clinical and laboratory routine HCWs will be trained including on the latest point of care (POC) diagnostic tests and safe administration of essential medicines for HIV-associated meningo-encephalitis such as amphotericin B deoxycholate using a Train the Trainer approach. The knowledge and skills will be disseminated widely following this training by frontline HCWs. Locally adapted optimal clinical and laboratory pathways for the diagnosis and treatment of HIV-related meningoencephalitis in resource limited settings will be devised during the training phase using a health system engineering approach.
- Implementation: Implementation of an algorithmic approach to diagnosis and treatment of HIV-associated meningitis including aggressive microbiological detection and treatment of cryptococcosis and tuberculosis in the five study sites. The aim is to reduce the time from participant presentation to diagnostic testing and administration of effective, microbiologically-driven treatment. As part of the implementation of the algorithm, the optimised clinical and laboratory pathways endorsed by local leadership are implemented. Communities of practice are formed with weekly multidisciplinary meetings to discuss clinical cases and continue laboratory capacity building.
The data from the observation and implementation phases of the study will be fed back to local ministries of health (MOH), and access to essential antifungal drugs and diagnostic tests for HIV-associated meningitis improved and finally, cohesive HIV-related meningitis guidelines for African LMICs developed.
Important sub-studies include a health economics evaluation study to determine the cost of the intervention and routine care costs. A new semi-quantitative cryptococcal antigen lateral flow assay (CrAg LFA) (CryptoPS, Biosynex, Strasburg, France) will be evaluated uniquely for the diagnosis of patients with meningo-encephalitis. New, POC polyvalent tests (CrAg/HIV) and (CrAg/Streptococcus pneumoniae) will also be evaluated.
These POC tests nested within algorithms, and the new tests being evaluated, together with administration of recommended, microbiologically driven treatments have the potential to significantly reduce CNS infection-related mortality by reducing delays in proven diagnosis and initiation of effective treatments.
Study design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Cohort study with a before and after design
| Arm | Type | Receives |
|---|---|---|
| DREAMM | Other | Other: DREAMM4 DREAMM interventions to reduce HIV-related meningoencephalitis mortality once access to essential diagnostic tests and medicines: 1. Health system strengthening 2. Delivery of a co-designed education program tailored to frontline healthcare workers 3. Implementation of an algorithm for HIV-related meningoencephalitis 4. Infectious diseases/AHD mentorship and laboratory capacity building |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Consecutive patients > 18 years with 1st episode of suspected meningo- encephalitis
- Known to be HIV positive or willing to undertake an HIV test
- Willing to agree to participate in the study
Key exclusion criteria (6 listed)
- Patients presenting with suspected relapse of HIV-associated meningo-encephalitis
- HIV negative patients
- Pregnant or lactating patients
- Patients presenting with a known diagnosis of primary CNS Lymphoma or cerebral malaria
- COVID-19 infected patients
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 |
|---|---|---|
| DREAMM4 DREAMM interventions to reduce HIV-related meningoencephalitis mortality once access to essential diagnostic tests and medicines: 1. Health system strengthening 2. Delivery of a co-designed education program tailored to frontline healthcare workers 3. Implementation of an algorithm for HIV-related meningoencephalitis 4. Infectious diseases/AHD mentorship and laboratory capacity building | Other | DREAMM |
Primary outcome
2-week all-cause mortality
Time frame: 2 weeks from enrolment
2-week all-cause mortality from enrolment
8 secondary outcomes
10-week all-cause mortality
Time frame: 10 weeks from enrolment
4-week all-cause mortality
Time frame: 4 weeks from enrolment
10-week and 6-month rate of death
Time frame: 10 weeks and 6 months from enrolment
Time to appropriate investigation: lumbar puncture, brain imaging
Time frame: 10 weeks from enrolment
Time to appropriate, microbiologically guided treatment
Time frame: 10 weeks from enrolment
Prevalence of cryptococcal, tuberculous and bacterial meningitis and toxoplasma meningo-encephalitis and neurosyphilis
Time frame: 10 weeks from enrolment
Time to ART initiation
Time frame: 10 weeks from enrolment
6-month all-cause mortality
Time frame: 6 months from enrolment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Derived from this study: PubMed 37802567Mfinanga S, Kanyama C, Kouanfack C, Nyirenda S, Kivuyo SL, Boyer-Chammard T, Phiri S, Ngoma J, Shimwela M, Nkungu D, Fomete LN, Simbauranga R, Chawinga C, Ngakam N, Heller T, Lontsi SS, Aghakishiyeva E, Jalava K, Fuller S, Reid AM, Rajasingham R, Lawrence DS, Hosseinipour MC, Beaumont E, Bradley J, Jaffar S, Lortholary O, Harrison T, Molloy SF, Sturny-Leclere A, Loyse A; DREAMM Consortium. Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study. Lancet HIV. 2023 Oct;10(10):e663-e673. doi: 10.1016/S2352-3018(23)00182-0.
Related trials for AIDS-Related Opportunistic Infections
Not yet recruiting
Enhanced Treatment Strategy for Disseminated MAC Infection in HIV Patients: A Randomized Controlled Trial
Opportunistic Infections, HIV Related, Disseminated Mycobacterium Avium Complex Infection
Not yet recruitingPhase 1/2
Efficacy and Safety of Immune Checkpoint Inhibitors for Refractory Opportunistic Infections in AIDS
HIV, AIDS
Not yet recruitingObservational study
Real-world Cohort Study of Antiretroviral Therapy in HIV Patients With Opportunistic Infections
Opportunistic Infections, HIV Related
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.
Angela Loyse, MD principal investigator
St George's, University of London
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DREAMM in people with AIDS-Related Opportunistic Infections and Meningo-encephalitis, run by St George's, University of London at 5 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 3 inclusion and 6 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: finished, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Malawi, Tanzania, Cameroon. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
2-week all-cause mortality (time frame: 2 weeks from enrolment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03226379, which also lists 1 linked publication.
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 4 May 2022.