Pentoxifylline in Children With Malaria

NCT ID: NCT00133393

Last Updated: 2010-08-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2005-07-31

Brief Summary

The primary objectives of this study is to identify a safe, tolerable dose of pentoxifylline in children with cerebral malaria and to establish an acceptable pentoxifylline dosage regimen for use in multi center Phase II and Phase III studies.

Detailed Description

This is an open, prospective, dose-escalating study, designed to elucidate the pharmacokinetics, pharmacodynamics, safety, and tolerability of pentoxifylline in children of the ages greater than/equal to 9 months and less than/equal to 96 months with cerebral malaria. The study is designed to evaluate pentoxifylline as adjunct therapy in severe pediatric malaria by evaluating its toxicity and associated adverse events, and by establishing both an acceptable dose and the associated pharmacokinetic profile. The pharmacodynamic effects of four different dose levels (10, 20, 30, and 40 mg/kg/24 hours) will be accessed on the following biological, immunological, and parasitological parameters: cerebral blood flow velocity, tumor necrosis factor concentration, rosetting, coma resolution time, parasite clearance time, and fever clearance time. Due to the variability observed in the biological, immunological, and parasitological parameters under scrutiny, a control group of ten patients will be intercalated in the study (4 patients prior to enrollment of the first pentoxifylline recipient, 2 patients in-between each of the 3 dose escalations). As there is no information about the relationship of treatment duration to biological, immunological, and parasitological effects, treatment will continue for 72 hours, by which time peripheral parasitemia will have cleared in the majority of patients. The selection of the pentoxifylline dosage regimen for the larger, multi center Phase II and Phase III studies will be made on the basis of the maximum tolerated dose (based on clinical and laboratory observations) which minimizes the dose-related side-effects and adverse events (based on pharmacokinetics) while permitting maximum biological, immunological, and/or parasitological effects (pharmacodynamics).

Conditions

Plasmodium Falciparum Malaria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Pentoxifylline

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Children meeting all of the following criteria are eligible for inclusion in the study.

Age greater than or equal to 9 months and less than or equal to 96 months. Informed consent granted by parents/guardians (Appendix I).

Has cerebral malaria defined as all of the following:

peripheral parasitemia with asexual forms of P. falciparum; inability to localize a painful stimulus 30 minutes after correcting hypoglycemia (blood glucose less than 2.2 mmol/l) in patients who present with hypoglycemia 30 minutes after cessation of convulsive activity in patients who are convulsing on admission; no neck stiffness; no clinical evidence of pneumonia (no rales, no decreased breath sounds, no bronchial breathing).

Exclusion Criteria

Children with the following will not be enrolled in the study:

Hypotension: mean blood pressure less than 60 mmHg (mean blood pressure = diastolic blood pressure (mmHg) + 1/3 (systolic blood pressure

• diastolic blood pressure)). Thrombocytopenia: platelet count less than 50 x 10(to the ninth power)/l. Spontaneous bleeding noted in mouth, throat, nares, rectum, or a venipuncture site following adequate pressure.

Hematocrit < 20% OR hematocrit between 20-25% with parasitemia greater than 10%.

• Minimum Eligible Age: 9 Months
• Maximum Eligible Age: 96 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Locations

KEMRI Centre for Geographic Medicine Research

Kilifi, , Kenya

Countries

Kenya

Other Identifiers

00-021

Identifier Type: -

Identifier Source: org_study_id