Nitrite Infusion in Children With Malaria

NCT04289558 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: Pro00100364R01HL130763
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety of intravenous sodium nitrite in African children who have moderately severe malaria.

Conditions

Falciparum Malaria

Keywords

falciparum malaria; malaria; Africa; Duke; Tanzania; sodium nitrite; Phase I; infectious disease; hematology

Outcome Measures

Primary Outcomes (2)

• Safety as measured by number of subjects with at least one adverse event

  Adverse events will be assessed according to the NIH's Table for Grading the Severity of Adult and Pediatric Adverse Events. Events will be numerically graded 1-5; 1 being a mild event and 5 being death

  48 hours post infusion

• Percent change in microvascular function/activation for each of the 4 dosing levels by linear regression

  We will assess possible covariate relationships. A model will be developed that links the pharmacokinetics with the pharmacodynamic measures of endothelial function and activation

  48 hours post infusion

Study Arms (1)

Sodium Nitrite

EXPERIMENTAL

Single 60-minute intravenous infusion of sodium nitrite in 0.9% sodium chloride at up to 4 sequential dose levels (0.16, 0.32, 0.64 and 1.28 mcg/kg/minute)

Drug: Sodium Nitrite

Interventions

Sodium Nitrite DRUG

Single 60 minute infusion at 1 of 4 sequential dose levels (0.16, 0.32, 0.64 and 1.28 mcg/kg/minute). The dose amount will depend on when the participant enters the study

Sodium Nitrite

Eligibility Criteria

• Age: 4 Years - 10 Years
• Gender Eligibility Details: Presence of G6PD deficiency increases the risk of RBC hemolysis occurring with administration of sodium nitrite and occurrence of methemoglobinemia. G6PD deficiency is an X-linked trait, thus males are either positive or negative, while females can exhibit a range of deficiency with heterozygotes commonly having an intermediate level
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Provision of signed and dated informed consent from parent or legal guardian
• Males, \>4 to 10 years of age
• Body weight \> 12 kg
• Parasitemia with Plasmodium falciparum including:
• Positive rapid diagnostic test result: AND
• \>2,500 parasites/microliter by microscopy
• Diagnosis of MSM, as follows:
• Clinical syndrome consistent with malaria associated with documented fever (axillary temperature \>38C) or reported history of fever in the past 48 hours with no other cause present; AND
• Exhibiting no WHO warning signs or criteria for SM \[27\]
• A negative G6PD deficiency test (careSTART G6PD quantitative biosensor)
• Requires inpatient parenteral treatment because of inability to tolerate oral therapy
• Hemoglobin \> 8 g/dL (subjects with prior blood transfusion will be eligible).
• Systolic blood pressure \> 85 mmHg
• Baseline quantitative methemoglobin measurement less than 2%
• Creatinine less than the upper limit of normal

You may not qualify if:

• Female gender
• Diagnosis of severe malaria
• Presence of infection, or mixed infection, with non-falciparum strains of malaria
• Signs of severe malaria\[27\], including 1 or more of the following:
• impaired consciousness (Blantyre coma score \<3 in children)
• prostration
• multiple convulsions (\>2 within 24 hours)
• acidosis (base deficit \>8 mEq/L or bicarbonate \<15 mmol/L or lactate \> 5 mmol/L)
• hypoglycemia (blood glucose \< 40 mg/dL or \<2.2 mmol/L)
• severe anemia (Hb \< 5g/dL )
• renal impairment (serum creatinine \>265 uMol/L or 3 mg/dL; or blood urea \>20 mmol/L)
• jaundice (bilirubin \>50 umol or 3 mg/dL with parasite count \>100000/ µL)
• pulmonary edema (including O2sat \<92% with RR \>30/min)
• circulatory collapse or shock
• significant bleeding

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Hubert Kairuki Memorial University

Dar es Salaam, Tanzania

Location

MeSH Terms

Conditions

Malaria, Falciparum; Malaria; Communicable Diseases

Interventions

Sodium Nitrite

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: February 28, 2020
• Study Start: June 1, 2021
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: March 16, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

TA (1)