AzTrials
AzTrials

Falciparum MalariaPhase 1NCT04289558

Nitrite Infusion in Children With Malaria

A Phase 1 study testing Sodium Nitrite in people with Falciparum Malaria, run by Duke University at 1 site in Tanzania.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 4 to 10 years, men only
Conditions the study is for
Falciparum Malaria
What is being tested?
Sodium Nitrite
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteTanzania
Study dates
1 Jun 2021to 1 Oct 2021
Phase
Phase 1
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 4 to 10 years
  • Men only
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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
Show all 25Show fewer
  • 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%)
  • Presence of concomitant non-malarial infection
  • Known G6PD deficiency
  • Known chronic illness including renal, cardiac, pulmonary, epilepsy
  • History of a reaction to a substance or medication consisting of dyspnea and cyanosis
  • History of trauma or bleeding in the 2 weeks prior to presentation
  • Clinical impression of disseminated intravascular coagulation
  • Subjects treated with parenteral anti-malarial drugs for more than 12 hours
  • Current use of drugs with oxidative potential (e.g., nitrates, dapsone, primaquine); or drugs that cause hypotension.
  • Known allergic reactions to sodium nitrite injection

Trial locations and contacts

1 site in 1 country.

Tanzania1 site

  • Hubert Kairuki Memorial University

    Dar es Salaam

Other trials in Tanzania

About this study

Official title: 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.

Read the detailed description

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.

Being tested
Sodium Nitrite
Keywords
falciparum malaria, malaria, Africa, Duke, Tanzania, sodium nitrite, Phase I, infectious disease, hematology
Medical subject headings
Malaria, Falciparum, Malaria, Communicable Diseases

What participants receive

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

  • Sodium NitriteDrug

    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

Study groups in NCT04289558
Study groupRoleWhat they receive
Sodium NitriteExperimentalSingle 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)
Receives: Drug: Sodium Nitrite

What is being measured

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

  1. 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

    Measured: 48 hours post infusion

  2. 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

    Measured: 48 hours post infusion

Timeline

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

  1. First posted28 Feb 2020
  2. Study start1 Jun 2021 (estimated)
  3. Primary completion1 Oct 2021 (estimated)
  4. Study completion1 Oct 2021 (estimated)

Why it stopped: current grant expiration in May, insufficient funds remaining, travel restrictions, COVID-19 restrictions in Tanzania, etc.

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04289558
Sponsor's protocol ID
Pro00100364
Other IDs
R01HL130763
Status last verified
Jan 2021
First submitted
27 Feb 2020
Last updated
16 Mar 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Sodium Nitrite in people with Falciparum Malaria, run by Duke University at 1 site in Tanzania.

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 15 inclusion and 25 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: withdrawn, as of the sponsor's last update on 16 Mar 2021. 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 Tanzania. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Safety as measured by number of subjects with at least one adverse event (time frame: 48 hours post infusion). The study lists 2 primary outcomes in all. 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 NCT04289558.

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 16 Mar 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in