Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT04289558
Other study ID # Pro00100364
Secondary ID R01HL130763
Status Withdrawn
Phase Phase 1
First received
Last updated
Start date June 1, 2021
Est. completion date October 1, 2021

Study information

Verified date January 2021
Source Duke University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date October 1, 2021
Est. primary completion date October 1, 2021
Accepts healthy volunteers No
Gender Male
Age group 4 Years to 10 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
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

Locations

Country Name City State
Tanzania Hubert Kairuki Memorial University Dar es Salaam

Sponsors (2)

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

Country where clinical trial is conducted

Tanzania, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
See also
  Status Clinical Trial Phase
Completed NCT00440752 - The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance N/A
Completed NCT01144702 - Effectiveness of the Association Artesunate and Mefloquine in the Treatment of Malaria by Plasmodium Falciparum Phase 2/Phase 3
Terminated NCT00400101 - Phase Ia Malaria Vaccine Trial of Two Virosome-Formulated Peptides Phase 1
Completed NCT01350856 - Tracking Resistance to Artemisinin (TRAC) Phase 4
Completed NCT00859807 - A Bioequivalence Study Comparing Camoquin® Suspension (Pfizer) To Flavoquine® Tablets (Sanofi Aventis) In Healthy Subjects Phase 4
Completed NCT04222088 - TES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014
Completed NCT01115439 - Artesunate+Sulfadoxine-Pyrimethamine for the Treatment of Uncomplicated Falciparum Malaria N/A
Completed NCT00282919 - A Three Day Trial of Azithromycin Plus Chloroquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria Phase 2
Completed NCT04422015 - Biological Mechanisms in Afebrile P. Falciparum Malaria
Completed NCT00894660 - A Bioequivalence Study Comparing Amodiaquine Tablet (Pfizer) To Amodiaquine Tablets (Arsuamoon-Guilin China) In Healthy Subjects Phase 1
Completed NCT00894374 - Bioequivalence Study Comparing Artesunate Tablet To Arsuamoon® Tablets (Guilin-China) In Healthy Subjects Phase 1
Completed NCT00493363 - Clinical Investigation of In-vivo Susceptibility of P.Falciparum to Artesunate in Western Cambodia N/A
Completed NCT00158548 - ACT With Chloroquine, Amodiaquine & Sulphadoxine-pyrimethamine in Pakistan Phase 3
Completed NCT01374126 - Azithromycin Combination Therapy for the Treatment of Severe Malaria Phase 2
Completed NCT00722150 - Artemisinin Resistance in Cambodia II N/A
Completed NCT00157833 - A Randomized Trial of Coartemether and Artekin for the Treatment of Uncomplicated Malaria in Papua, Indonesia. N/A
Completed NCT00513669 - Phase Ib Trial of Two Virosome Formulated Malaria Vaccine Components (PEV 301, PEV 302) in Tanzania Phase 1
Completed NCT00403260 - Pyronaridine - Artesunate (3:1) Versus Mefloquine Plus Artesunate in Plasmodium Falciparum Malaria Patients Phase 3
Completed NCT00442377 - Study to Investigate the Induction of an Protective Immune Response to Malaria N/A
Completed NCT01365598 - Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda Phase 3