Rosiglitazone Adjunctive Therapy for Severe Malaria in Children

NCT02694874 | Completed

• 1 other identifier: ROSI_v03_22072015
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Malaria

Keywords

Adjunctive treatment; Severe malaria

Outcome Measures

Primary Outcomes (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

  first 96 hours of hospital admission.

Secondary Outcomes (10)

• Time to clinical recovery

  up to 96 hours after hospital admission

• Time to parasitological recovery

  up to 96 hours after hospital admission

• Mortality

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

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

• 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

Study Arms (2)

Rosiglitazone

EXPERIMENTAL

Participants will receive rosiglitazone 0.045mg/kg/dose twice daily dosing, for 4 days

Drug: Rosiglitazone

Placebo

PLACEBO COMPARATOR

Participants will receive placebo (grounded placebo powder) at a dose of 0.045mg/kg/dose twice daily for 4 days

Drug: Placebo

Interventions

Rosiglitazone DRUG

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

Also known as: Avandia

Rosiglitazone

Placebo DRUG

This is the placebo control

Also known as: crushed powder placebo

Placebo

Eligibility Criteria

• Age: 12 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centro de Investigacao em Saude de Manhica: lead
• University Health Network, Toronto: collaborator
• Barcelona Institute for Global Health: collaborator

Study Sites (1)

Centro de Investigação em Saude da Manhiça

Manhiça, Maputo Province, CP1929, Mozambique

Location

Related Publications (2)

• 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.

  PMID: 38013152 RESULT

• 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.

  PMID: 28535809 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Eusebio Macete, PhD

  Fundaçao Manhiça

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: March 1, 2016
• Study Start: February 1, 2016
• Primary Completion: March 1, 2020
• Study Completion: December 1, 2021
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

MO (1)