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Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM)

Primary Purpose

AIDS-Related Opportunistic Infections, Meningo-encephalitis, Cryptococcal Meningitis

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
DREAMM
Sponsored by
St George's, University of London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for AIDS-Related Opportunistic Infections focused on measuring HIV related Meningitis, AIDS-Related Opportunistic Infections, Advanced HIV Disease, Health Systems Strengthening, Education Programmes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Consecutive patients > 18 years with 1st episode of suspected meningo- encephalitis
  2. Known to be HIV positive or willing to undertake an HIV test
  3. Willing to agree to participate in the study

Exclusion Criteria:

  1. Patients presenting with suspected relapse of HIV-associated meningo-encephalitis
  2. HIV negative patients
  3. Pregnant or lactating patients
  4. Patients presenting with a known diagnosis of primary CNS Lymphoma or cerebral malaria
  5. 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or are diagnosed with cerebral malaria on hospital admission or after initial investigation will be excluded or withdrawn from the DREAMM study.

Sites / Locations

  • Hôpital Central Yaoundé
  • Kamuzu Central Hospital
  • Zomba Central Hospital
  • Amana Hospital
  • Mwananyamala Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

DREAMM

Arm Description

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

Outcomes

Primary Outcome Measures

2-week all-cause mortality
2-week all-cause mortality from enrolment

Secondary Outcome Measures

10-week all-cause mortality
10-week all-cause mortality from enrolment
4-week all-cause mortality
4-week all-cause mortality 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
Time to appropriate investigation: lumbar puncture, brain imaging
Time to appropriate investigation: lumbar puncture, brain imaging 10 weeks from enrolment
Time to appropriate, microbiologically guided treatment
Time to appropriate, microbiologically guided treatment 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
Time to ART initiation
Time to ART initiation 10 weeks from enrolment
6-month all-cause mortality
6-month all-cause mortality 6 months from enrolment

Full Information

First Posted
May 31, 2017
Last Updated
May 3, 2022
Sponsor
St George's, University of London
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
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1. Study Identification

Unique Protocol Identification Number
NCT03226379
Brief Title
Driving Reduced AIDS-associated Meningo-encephalitis Mortality
Acronym
DREAMM
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
April 23, 2016 (Actual)
Primary Completion Date
April 2021 (Actual)
Study Completion Date
September 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St George's, University of London
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
Cohort study with a before and after design
Masking
None (Open Label)
Allocation
N/A
Enrollment
495 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DREAMM
Arm Type
Other
Arm Description
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
Intervention Type
Other
Intervention Name(s)
DREAMM
Intervention Description
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
Primary Outcome Measure Information:
Title
2-week all-cause mortality
Description
2-week all-cause mortality from enrolment
Time Frame
2 weeks from enrolment
Secondary Outcome Measure Information:
Title
10-week all-cause mortality
Description
10-week all-cause mortality from enrolment
Time Frame
10 weeks from enrolment
Title
4-week all-cause mortality
Description
4-week all-cause mortality 4 weeks from enrolment
Time Frame
4 weeks from enrolment
Title
10-week and 6-month rate of death
Description
10-week and 6-month rate of death 10 weeks and 6 months from enrolment
Time Frame
10 weeks and 6 months from enrolment
Title
Time to appropriate investigation: lumbar puncture, brain imaging
Description
Time to appropriate investigation: lumbar puncture, brain imaging 10 weeks from enrolment
Time Frame
10 weeks from enrolment
Title
Time to appropriate, microbiologically guided treatment
Description
Time to appropriate, microbiologically guided treatment 10 weeks from enrolment
Time Frame
10 weeks from enrolment
Title
Prevalence of cryptococcal, tuberculous and bacterial meningitis and toxoplasma meningo-encephalitis and neurosyphilis
Description
Prevalence of cryptococcal, tuberculous and bacterial meningitis and toxoplasma 10 weeks from enrolment
Time Frame
10 weeks from enrolment
Title
Time to ART initiation
Description
Time to ART initiation 10 weeks from enrolment
Time Frame
10 weeks from enrolment
Title
6-month all-cause mortality
Description
6-month all-cause mortality 6 months from enrolment
Time Frame
6 months from enrolment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angela Loyse, MD
Organizational Affiliation
St George's, University of London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Central Yaoundé
City
Yaoundé
Country
Cameroon
Facility Name
Kamuzu Central Hospital
City
Lilongwe
Country
Malawi
Facility Name
Zomba Central Hospital
City
Zomba
Country
Malawi
Facility Name
Amana Hospital
City
Dar es Salaam
Country
Tanzania
Facility Name
Mwananyamala Hospital
City
Dar es Salaam
Country
Tanzania

12. IPD Sharing Statement

Learn more about this trial

Driving Reduced AIDS-associated Meningo-encephalitis Mortality

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