A Retrospective Analysis of Suramin Treatment for Stage 1 TBR

A Retrospective Analysis of Suramin Treatment for Stage 1 Trypanosoma Brucei Rhodesiense Human African Trypanosomiasis (S1 TBR HAT) in Uganda and Malawi

The study will include TBR HAT patients treated with suramin between 2000 and 2020 at three sites in Uganda and Malawi A natural history cohort composed of source data from approximately 200 patients from a published epidemiological study will be used as a comparator.

This study's objectives are to evaluate the efficacy and safety of suramin in the Stage 1 treatment of TBR HAT.

Study Overview

• Status: Completed
• Conditions: Trypanosoma Brucei Rhodesiense; Infection

Detailed Description

The study will include TBR HAT patients treated with suramin between 2000 and 2020 at three sites in Uganda and Malawi (e.g., the retrospective suramin-treated cohort). The study will include all the approximately 145 patients who are deemed eligible through chart review and who have sufficient data. A natural history cohort composed of source data from approximately 200 patients from a published epidemiological study will be used as a comparator.

The primary objective is to determine whether standard of care treatment with suramin, as currently practiced in Uganda and Malawi, leads to better health outcomes in patients with S1 TBR HAT than observed in a natural history cohort with source data from a published epidemiologic study.

• Study Type: Observational
• Enrollment (Actual): 345

Contacts and Locations

Study Locations

• United States
  • New York
    • Tarrytown, New York, United States, 10591
      • PaxMedica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patient charts will be retrieved from three major TBR HAT treatment centers. The study will include approximately 145 patients with S1TBR HAT who have sufficient clinical data for analysis. The study will also include a natural history cohort of the eligible subset of the approximately 200 patients from the 1900-1920 TBR HAT epidemic who were hospitalized in the years 1901 through 1910; some of these patients received experimental treatments such as arsenic which may have had some temporary clinical improvement, but none received any treatment with demonstrated efficacy.

Description

Inclusion Criteria:

• Suramin-treated cohort:

  • Patient records must meet all the following criteria to be included in the suramin-treated cohort:
  • Male or female of any age; age or sex must be included.
  • Treatment with at least four full doses of suramin (not including the test dose).
  • Onset date or duration of symptoms associated with S1 TBR HAT is available.
  • An outcome is required; any mention of a clinical outcome is acceptable.
  • Must live in an area endemic for TBR HAT
  • Documented HAT diagnosis
  • Positive parasitology for HAT (observed in blood sample or a standard test).

Natural History cohort:

• Treatment records from a cohort of approximately 200 patients who were hospitalized between 1901 and 1910 during the 1900-1920 HAT epidemic

• Treatment records must have sufficient information for analysis including:

  • Demographic data: age or sex must be included
  • Diagnosis: HAT diagnosis is confirmed by blood or lymph gland fluid analysis and parasites observed or HAT symptoms during the epidemic. For example, if the records state that a lymph node biopsy was performed, any result of the biopsy (e.g., documentation that trypanosomes were observed), a documentation of the HAT diagnosis, or mention of HAT symptoms such as sleepiness or excess sleeping are all acceptable. Symptoms alone are not sufficient, but a notation of biopsy and mention of HAT symptoms is acceptable.
  • Outcome: An outcome is required; any mention of a clinical outcome is acceptable.

Exclusion Criteria:

Patient records that meet any of the following criteria will be excluded from the suramin-treated cohort:

• Reported duration of symptoms for more than 2 months at time of presentation at a healthcare facility.
• Stage 2 TBR HAT as determined by examination of cerebrospinal fluid (CSF) using WHO criteria, which classify patients with the presence of trypanosomes in the CSF and/or a WBC count >5 cells/mm3 as Stage 2 TBR HAT at time of presentation to a healthcare facility.
• Evidence of Stage 2 TBR HAT symptoms at time of presentation to a healthcare facility.
• Required medication treatment for Stage 2 illness (melarsoprol) prior to time of presentation to a healthcare facility.
• Known to have had Trypanosoma Brucei Gambiense (TBG) HAT or became ill while travelling from an area known to be endemic for TBG HAT
• Duration of HAT symptoms for more than 6 months. Survival for more than 6 months with TBR HAT is unlikely.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Natural History Cohort: Treatment records from a cohort of approximately 200 patients who were hospitalized between 1901 and 1910 during the 1900-1920 HAT epidemic; Treatment records must have sufficient information for analysis including:Demographic data: age or sex must be includedDiagnosis: HAT diagnosis is confirmed by blood or lymph gland fluid analysis and parasites observed or HAT symptoms during the epidemic. For example, if the records state that a lymph node biopsy was performed, any result of the biopsy (e.g., documentation that trypanosomes were observed), a documentation of the HAT diagnosis, or mention of HAT symptoms such as sleepiness or excess sleeping are all acceptable. Symptoms alone are not sufficient, but a notation of biopsy and mention of HAT symptoms is acceptable.Outcome: An outcome is required; any mention of a clinical outcome is acceptable.
Retrospective cohort; The hospital records of TBR HAT patients will be examined for date of symptom onset (if available) and hospital admission, race, sex, age, geographic area of origin, parasites, concomitant medications and illnesses, co-infections, and disease stage. Patients are normally screened for HAT and other tropical diseases using standard parasitological World Health Organization (WHO) criteria. Briefly, blood is obtained from the patients and checked for the presence of trypanosomes using direct wet smear and capillary centrifugation technique methods. Disease stage determination is by examination of CSF using the WHO criteria which classify patients with the presence of trypanosomes in the CSF and/or a WBC count >5 cells/mm3 as Stage 2 TBR HAT. Stage 2 patients would be disqualified from inclusion in the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary efficacy endpoint is survival of patients treated with suramin compared to the natural history cohort.	The primary efficacy analysis will compare the proportion alive and not meeting any of the following criteria; Death (both cohorts).; Progression from Stage 1 to Stage 2 TBR HAT as defined by meeting any of the following:presence of TBR trypanosomes in the cerebrospinal fluid (CSF)abnormal symptoms .presence of TBR HAT symptoms for more than 2 monthsUse of melarsoprol for clinical worsening or treatment failure; Moribund status	30 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The secondary objective is to describe the safety and tolerability of suramin.	• Incidence of adverse events.	30 Days

Collaborators and Investigators

• Sponsor: Paxmedica
• Investigators: Study Director: jennifer L bonfrisco, PaxMedica

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2023
• Primary Completion (Actual): August 2, 2023
• Study Completion (Actual): August 2, 2023

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Trypanosomiasis; Euglenozoa Infections; Trypanosomiasis, African
• Other Study ID Numbers: PAX-HAT-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No