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Nitrite Infusion in Children With Malaria

12. marts 2021 opdateret af: Duke University

Safety, Feasibility, and Endothelial Effects of Sodium Nitrite Infusion in Children With Falciparum Malaria

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

Studieoversigt

Status

Trukket tilbage

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This is a Phase I, open-label, dose-escalation study that will enroll up to 24 patients total, using a 3+3 dose escalation design, with 3 to 6 patients per dose level at up to 4 sequential dose levels (0.16, 0.32, 0.64 and 1.28 mcg/kg/minute). At each dose level patients with moderately severe malaria will receive a single 60-minute intravenous infusion of sodium nitrite in 0.9% sodium chloride. Blood pressure and methemoglobin levels will be closely monitored during the infusion and for 24 hours post infusion.

This study will allow a preliminary analysis of the safety of intravenous sodium nitrite in children with moderately severe malaria and is expected to provide preliminary data on its effects on endothelial function. The hypothesis is that sodium nitrite infusion will be safe at low dosage levels. Additionally, since deficiency of nitric oxide is linked to endothelial dysfunction in malaria, there is the hypothesis that sodium nitrite will result in improved markers of endothelial function.

Children are the largest group affected by falciparum malaria. The study population will be male children residing in Tanzania, ages 4-10 years old diagnosed with moderately severe malaria, who have been hospitalized for treatment of their malaria at Hubert Kairuki Medical University in Dar es Salaam, Tanzania. Patients will receive standard anti-malaria and supportive care treatment. The study will enroll up to 24 subjects.

Participants will receive a single intravenous infusion of sodium nitrite diluted in 0.9% sodium chloride. The infusion will be administered over 60 minutes with an infusion pump. Escala-ting doses of sodium nitrite will be administered to patients in 4 dose level cohorts. Patients will be sequentially enrolled starting at the lowest dose level. Individual patients at the same dose level will also be enrolled sequentially, such that the next patient will not receive treatment until completion of a 24- hour safety monitoring period for the prior patient. Dose assign-ment will be based on the order of study enrollment. The maximum tolerated dose (MTD) is the highest dose level wherein ≤ 1 of 6 evaluable patients experiences dose limiting toxicity (DLT). If the MTD is exceeded at the first dose level, then dosing will cease.

Undersøgelsestype

Interventionel

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Tanzania
      • Dar es Salaam, Tanzania
        • Hubert Kairuki Memorial University

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

4 år til 10 år (Barn)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Han

Beskrivelse

Inclusion Criteria:

  1. Provision of signed and dated informed consent from parent or legal guardian
  2. Males, >4 to 10 years of age
  3. Body weight > 12 kg

  4. Parasitemia with Plasmodium falciparum including:

    1. Positive rapid diagnostic test result: AND
    2. >2,500 parasites/microliter by microscopy

  5. Diagnosis of MSM, as follows:

    1. 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
    2. Exhibiting no WHO warning signs or criteria for SM [27]
  6. A negative G6PD deficiency test (careSTART G6PD quantitative biosensor)
  7. Requires inpatient parenteral treatment because of inability to tolerate oral therapy
  8. Hemoglobin > 8 g/dL (subjects with prior blood transfusion will be eligible).
  9. Systolic blood pressure > 85 mmHg
  10. Baseline quantitative methemoglobin measurement less than 2%
  11. Creatinine less than the upper limit of normal

Exclusion Criteria:

  1. Female gender
  2. Diagnosis of severe malaria
  3. Presence of infection, or mixed infection, with non-falciparum strains of malaria

  4. 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
    • hyperparasitemia (>10%)
  5. Presence of concomitant non-malarial infection
  6. Known G6PD deficiency
  7. Known chronic illness including renal, cardiac, pulmonary, epilepsy
  8. History of a reaction to a substance or medication consisting of dyspnea and cyanosis
  9. History of trauma or bleeding in the 2 weeks prior to presentation
  10. Clinical impression of disseminated intravascular coagulation
  11. Subjects treated with parenteral anti-malarial drugs for more than 12 hours
  12. Current use of drugs with oxidative potential (e.g., nitrates, dapsone, primaquine); or drugs that cause hypotension.
  13. Known allergic reactions to sodium nitrite injection

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Sodium Nitrite
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)
Medicin: Sodium Nitrite
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

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Safety as measured by number of subjects with at least one adverse event
Tidsramme: 48 hours post infusion
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
Tidsramme: 48 hours post infusion
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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Duke University

Samarbejdspartnere

National Heart, Lung, and Blood Institute (NHLBI)

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Forventet)

1. juni 2021

Primær færdiggørelse (Forventet)

1. oktober 2021

Studieafslutning (Forventet)

1. oktober 2021

Datoer for studieregistrering

Først indsendt

27. februar 2020

Først indsendt, der opfyldte QC-kriterier

27. februar 2020

Først opslået (Faktiske)

28. februar 2020

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

16. marts 2021

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

12. marts 2021

Sidst verificeret

1. januar 2021

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • Pro00100364
  • R01HL130763 (U.S. NIH-bevilling/kontrakt)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ja

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Kliniske forsøg med Falciparum malaria

Kliniske forsøg med Sodium Nitrite

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Ireland

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

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