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

May 3, 2022 updated by: St George's, University of London

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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:

  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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
495

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Cameroon
      • Yaoundé, Cameroon
        • Hopital Central Yaoundé
  • Malawi
      • Lilongwe, Malawi
        • Kamuzu Central Hospital
      • Zomba, Malawi
        • Zomba Central Hospital
  • Tanzania
      • Dar es Salaam, Tanzania
        • Amana Hospital
      • Dar es Salaam, Tanzania
        • Mwananyamala Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: DREAMM

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
Other: DREAMM

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
2-week all-cause mortality
Time Frame: 2 weeks from enrolment
2-week all-cause mortality from enrolment
2 weeks from enrolment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
10-week all-cause mortality
Time Frame: 10 weeks from enrolment
10-week all-cause mortality from enrolment
10 weeks from enrolment
4-week all-cause mortality
Time Frame: 4 weeks from enrolment
4-week all-cause mortality 4 weeks from enrolment
4 weeks from enrolment
10-week and 6-month rate of death
Time Frame: 10 weeks and 6 months from enrolment
10-week and 6-month rate of death 10 weeks and 6 months from enrolment
10 weeks and 6 months from enrolment
Time to appropriate investigation: lumbar puncture, brain imaging
Time Frame: 10 weeks from enrolment
Time to appropriate investigation: lumbar puncture, brain imaging 10 weeks from enrolment
10 weeks from enrolment
Time to appropriate, microbiologically guided treatment
Time Frame: 10 weeks from enrolment
Time to appropriate, microbiologically guided treatment 10 weeks from enrolment
10 weeks from enrolment
Prevalence of cryptococcal, tuberculous and bacterial meningitis and toxoplasma meningo-encephalitis and neurosyphilis
Time Frame: 10 weeks from enrolment
Prevalence of cryptococcal, tuberculous and bacterial meningitis and toxoplasma 10 weeks from enrolment
10 weeks from enrolment
Time to ART initiation
Time Frame: 10 weeks from enrolment
Time to ART initiation 10 weeks from enrolment
10 weeks from enrolment
6-month all-cause mortality
Time Frame: 6 months from enrolment
6-month all-cause mortality 6 months from enrolment
6 months from enrolment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
St George's, University of London

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Institut Pasteur
European and Developing Countries Clinical Trials Partnership (EDCTP)
National Institute for Medical Research, Tanzania
National Agency for Research on AIDS and Viral Hepatitis (ANRS)
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

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Angela Loyse, MD, St George's, University of London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 23, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 31, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 21, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16.0091

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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