AzTrials
AzTrials

MalariaROSINCT02694874

Rosiglitazone Adjunctive Therapy for Severe Malaria in Children

A study testing Rosiglitazone in people with Malaria, run by Centro de Investigacao em Saude de Manhica at 1 site in Mozambique.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Even with optimal anti-malaria therapy and supportive care, severe and cerebral malaria are associated with a 10-30% mortality rate and neurocognitive deficits in up to 33% of survivors. Read more about this study

Who is it for?
Ages 12 months to 12 years
Conditions the study is for
Malaria
What is being tested?
Rosiglitazone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
210 participants
Where
1 siteMozambique
Study dates
Feb 2016to Dec 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 12 months to 12 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Age 1-12 years
  • Positive 3-band (HRPII plus pLDH) P. falciparum rapid diagnostic test (RDT) and microscopy confirmed malaria infection with parasitemia >2500 parasites/microlitre if microscopy is available in a timely manner at the time of randomization.
  • One or more features of severe malaria: repeated seizures (two or more generalized seizures in 24 h); prostration (in children 1 year and older, the child is unable to sit unsupported or stand although was able to before the illness); impaired consciousness (Blantyre Coma Score <5 in children 1 to 4 years, GCS <14 for children ≥ 5 years); respiratory distress: age related tachypnea with sustained nasal flaring, deep breathing or subcostal retractions
  • Requiring hospitalization and parenteral artesunate for their malaria infection based on admitting physician assessment

Who cannot join

  • P. falciparum RDT negative OR infection not confirmed by light microscopy or not reaching the predefined inclusion criterion parasitemia threshold according to age
  • Uncomplicated malaria infection not requiring hospitalization
  • Presenting with severe malaria anemia (SMA) alone (Hb < 50g/L)
  • Known underlying illness: neurological or neurodegenerative disorders, cardiac, renal, or hepatic disease, diabetes, epilepsy, cerebral palsy, children known to be HIV-1 positive and receiving antiretroviral treatment*
  • Previous treatment with a TZD
  • Unable to remain in research site region for the follow up period

Trial locations and contacts

1 site in 1 country.

Mozambique1 site

  • Centro de Investigação em Saude da Manhiça

    Manhiça, Maputo Province, CP1929

Other trials in Mozambique

About this study

Even with optimal anti-malaria therapy and supportive care, severe and cerebral malaria are associated with a 10-30% mortality rate and neurocognitive deficits in up to 33% of survivors. Adjunctive therapies that modify host immune-pathological processes may further improve outcome over that possible with anti-malarials alone. Investigators aim to evaluate a PPARγ agonist ( "rosiglitazone") as adjunctive therapy for severe malaria.

Read the detailed description

Although the use of artemisinin-based therapy has improved outcomes in severe malaria, the mortality rates remain high. Adjunctive therapies that target the underlying immunopathology may further reduce morbidity and mortality in severe and cerebral malaria beyond that possible with anti-malarials alone. Pre-clinical data have established a beneficial role for PPARγ agonists in experimental cerebral malaria. A proof-of-concept randomized clinical trial of uncomplicated malaria in Thailand has extended these findings to an informative patient population, showing that adjunctive treatment with the PPARγ agonist rosiglitazone improves parasite clearance, and reduces biomarkers of inflammation (IL-6 and MCP-1) and endothelial activation (Ang-2 to Ang-1 ratio), and increases neuro-protective pathways (BDNF). The previous clinical trial also established the safety and tolerability of short course rosiglitazone in adults with malaria infection. Importantly, rosiglitazone does not induce insulin release or hypoglycemia in malaria-infected patients. Based on these data, and on studies demonstrating neuro-protective effects on PPARγ agonists in CNS disease and injury, the investigators believe that PPARγ agonists are promising candidates for adjunctive therapy for severe and cerebral malaria.

In this study the efficacy of rosiglitazone vs. placebo control as adjunct to standard of care anti-malarial therapy in children with severe (including cerebral) malaria will be tested.

The underlying hypothesis is that the addition of rosiglitazone to standard antimalarial therapy in severe P. falciparum infection is safe and will result in improved clinical outcomes and lower rates of long-term neurocognitive impairment.

Conditions
Malaria
Being tested
Rosiglitazone, Placebo
Keywords
Adjunctive treatment, Severe malaria
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RosiglitazoneDrug

    Also called Avandia

    This is the experimental drug, rosiglitazone, being tested against placebo to assess its efficacy as an adjunctive treatment for severe malaria

  • PlaceboDrug

    Also called crushed powder placebo

    This is the placebo control

Study groups in NCT02694874
Study groupRoleWhat they receive
RosiglitazoneExperimentalParticipants will receive rosiglitazone 0.045mg/kg/dose twice daily dosing, for 4 days
Receives: Drug: Rosiglitazone
PlaceboPlacebo comparatorParticipants will receive placebo (grounded placebo powder) at a dose of 0.045mg/kg/dose twice daily for 4 days
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in serum Ang-2 levels in the first 96 hours of hospital admission.

    We will assess the effect of the intervention (vs. placebo) on Ang-2 levels as a biomarker of severe disease in severe malaria

    Measured: first 96 hours of hospital admission.

Secondary outcomes (10)

  1. Time to clinical recovery

    Time to recovery including:

    1. Time to fever resolution for at least 24h. Temperature measurements will be taken at admission and every 4h for the first 4 days, and then every 12h until 2 normal results (<37.5oC) are reported.
    2. Time to sit unsupported
    3. Time to hospital discharge

    Measured: up to 96 hours after hospital admission

  2. Time to parasitological recovery

    Time to parasitological recovery: Time (in hours) to clearance of parasitemia from the blood (both 50% and 90% decrease from admission baseline value). Parasitemia will be quantified at admission and every 6h, for 4 days or until 2 negative readings are reported.

    Measured: up to 96 hours after hospital admission

  3. Mortality

    Mortality in the first 48h post-hospital admission and at 14 days post-hospital admission

    Measured: first 48h post-hospital admission and at 14 days post-hospital admission

  4. Blood lactate levels, assessed at admission, every 12h for 24 hours then daily for Blood lactate levels

    Blood lactate levels, assessed at admission, every 12h for 24 hours then daily for 4 days, and once on day 14 and 6 month follow ups

    Measured: Assessed at admission, every 12h for 24 hours then daily for 4 days, and once on day 14 and 6 month follow ups

  5. Change in levels of biomarkers of host response

    Change in levels of biomarkers of host response at admission, every 12h for 24 hours then daily for 4 days, and once on day 14 and 6 month follow ups

    Measured: at admission, every 12h for 24 hours then daily for 4 days, and once on day 14 and 6 month follow ups

  6. Blood glucose levels

    Blood glucose levels assessed at admission and every 6h for the first 48h, and then every 24h for following 2 days

    Measured: up to 96 hours after hospital admission

  7. Cardiac effects

    Monitor for cardiac effects by conducting ECG at baseline, at 24h (immediately before third doses of rosiglitazone and artesunate treatment are administered) and at the end of rosiglitazone treatment (day 4). Main outcome of interest will be changes in QTc from baseline to the two different time points.

    Measured: from baseline to 24h, and day 4

  8. Biochemical and hematological parameters

    Biochemical and hematological parameters including: AST, ALT, creatinine, complete blood count (e.g. hemoglobin, WBC and differential, hematocrit, platelet count) will be assessed at admission and every 24h until day 4

    Measured: up to 96 hours after hospital admission

  9. AE/SAE

    AE/SAE monitored using the pediatric toxicity tables modified from the US National Institutes of Allergy and Infectious Diseases

    Measured: up to day 14 after hospital admission

  10. Neurocognitive outcomes

    Participants with Adverse Events that Are Related and unrelated to Treatment by a variety of standard neurocognitive tests

    Measured: From baseline to 6 months post discharge, and 18 months post discharge

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2016 (estimated)
  2. Study startFeb 2016
  3. Primary completionMar 2020
  4. Study completionDec 2021

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
210 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02694874
Sponsor's protocol ID
ROSI_v03_22072015
Acronym
ROSI
Status last verified
Feb 2024
First submitted
9 Dec 2015
Last updated
21 Feb 2024
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Varo R, Crowley VM, Mucasse H, Sitoe A, Bramugy J, Serghides L, Weckman AM, Erice C, Bila R, Vitorino P, Mucasse C, Valente M, Ajanovic S, Balanza N, Zhong K, Derpsch Y, Gladstone M, Mayor A, Bassat Q, Kain KC. Adjunctive rosiglitazone treatment for severe pediatric malaria: A randomized placebo-controlled trial in Mozambican children. Int J Infect Dis. 2024 Feb;139:34-40. doi: 10.1016/j.ijid.2023.11.031. Epub 2023 Nov 25.

    PubMed 38013152

  • Varo R, Crowley VM, Sitoe A, Madrid L, Serghides L, Bila R, Mucavele H, Mayor A, Bassat Q, Kain KC. Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria. Malar J. 2017 May 23;16(1):215. doi: 10.1186/s12936-017-1858-0.

    PubMed 28535809

Questions about this trial

What is this clinical trial studying?

A study testing Rosiglitazone in people with Malaria, run by Centro de Investigacao em Saude de Manhica at 1 site in Mozambique.

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 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 21 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mozambique. 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. Some participants in this study may receive a placebo. 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?

Change in serum Ang-2 levels in the first 96 hours of hospital admission. (time frame: first 96 hours of hospital admission.). 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 NCT02694874, which also lists 2 linked publications.

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 21 Feb 2024.

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