Nitrite Infusion in Children With Malaria

• Status: Withdrawn
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: Male

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)

Criteria

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