Clinical trial NCT01814423: Pharmacokinetic Study of Multi-dose Chloroquine
Official title: Pharmacokinetic Study of Multi-dose Chloroquine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria
Keywords: Plasmodium falciparum
malaria
chloroquine
pharmacokinetic
children
Lead sponsor: Bandim Health Project
Sponsor class: OTHER
First posted: 2013-03-20
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Chloroquine (CQ) remains an alternative cheap, safe and widely available drug. Our previous research has shown that double (50 mg/kg) standard dose CQ given in split doses had a 95% efficacy and was well tolerated and safe. Still, safety could be an issue when the dose of CQ is increased. Severe adverse events are caused by high peak concentrations of CQ. Using split doses of CQ avoids high peak concentrations enabling the safe administration of high doses, however, pharmacokinetic data are lacking.

Children included in the study will be given 50 mg/kg as split doses over 3 days or 70 mg/kg as split doses over 5 days. Treatment will be observed. Drug concentrations and adverse events will be monitored. On day 1, children and their mother/guardian will be requested to stay at the health centre between 9 am and 6 pm.

Fifteen children aged 2-10 years with uncomplicated P. falciparum malaria and fulfilling the inclusion criteria will be recruited into each study arm.

Following the end of treatment, the children will be seen on the morning of day 7, 14, 21 and 28.

Any child wishing to withdraw during the treatment phase and any child with reparasitaemia during the follow up will be given rescue treatment with arthemeter-lumefantrine or quinine according to treatment guidelines in Guinea-Bissau.

Final analysis will include a description of included children, proportions of adverse events and any serious adverse events, drug concentrations and their relation to adverse events, the proportion of children withdrawn or lost to follow up, the cumulative PCR corrected and uncorrected success and failure rates on day 28 and the proportion of early, late clinical and late parasitological treatment failures.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 2 years and \< 10 years.
* Mono-infection with P. falciparum detected by microscopy. Parasitemia of 1.000-100.000/µl asexual forms.
* Axillary temperature ≥ 37.5 ˚C or a history of fever within 24 hours.
* Ability to swallow oral medication.
* Ability and willingness to comply with the study protocol.
* Informed consent from a parent or guardian

Exclusion Criteria:

* Signs or symptoms of severe malaria.
* Presence of general danger signs in children under 5.
* Persistent vomiting.
* Presence of severe malnutrition.
* Any evidence of chronic disease or acute infection other than malaria.
* Regular medication which may interfere with antimalarial pharmacokinetics.
* History of hypersensitivity reactions or contraindications to chloroquine.

Primary outcomes:
measure: Chloroquine serum concentration
timeFrame: Twice daily during treatment, on day 1 an additional 8 measurements.
Secondary outcomes:
measure: Parasitemia
timeFrame: Twice a day dúring treatment and then weekly until day 28.
Other outcomes:
measure: Haemoglobin level
timeFrame: On day 0, 3 and 28.
measure: Blood pressure
timeFrame: On day 1 and day 28
measure: ECG
timeFrame: Will be measures on day 1 and on last treatment day.
Locations:
city: Bissau
country: Guinea-Bissau
facility: Projecto de Saúde de Bandim
Study officials:
affiliation: Bandim Health Project
name: Poul-Erik Kofoed, Ph.d
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ursing J, Rombo L, Eksborg S, Larson L, Bruvoll A, Tarning J, Rodrigues A, Kofoed PE. High-Dose Chloroquine for Uncomplicated Plasmodium falciparum Malaria Is Well Tolerated and Causes Similar QT Interval Prolongation as Standard-Dose Chloroquine in Children. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01846-19. doi: 10.1128/AAC.01846-19. Print 2020 Feb 21.