Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03226379 |
| Other study ID # |
16.0091 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 23, 2016 |
| Est. completion date |
September 2021 |
Study information
| Verified date |
April 2022 |
| Source |
St George's, University of London |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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 building) when combined reduce two week all-cause
mortality of HIV-associated meningo-encephalitis in African LMICs.
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:
1. 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.
2. 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.
3. 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.
