Health Condition 1: null- Moderate to severe P. falciparum Malaria
Conditions
Interventions
Intervention1: sevuparin/DF02: Test Product and Dose : 3 mg/kg body weight sevuparin/DF02 Test Product and Dose : 3 mg/kg body weight sevuparin/DF02 given IV every 6hours until patient recovery or unt
Sponsors
Dilaforette AB
Max Neeman International
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female, 18 to 65 years old, inclusive 2. P. falciparum infection, confirmed by positive blood smear 3. Counts of asexual forms of P. falciparum >= 1,000 parasites/μl 4. Diagnosis of severe malaria according to WHO criteria for severe malaria 2010 (Appendix 19.3) or severe prostration (defined as extreme weakness,inability to walk or sit up without assistance or impaired consciousness with behavioural changes, confusion or drowsiness) 5. Written informed consent
Exclusion criteria
Exclusion criteria: 1. Jaundice (defined as total serum bilirubin >3 mg/dL) with no other clinical symptoms of severe malaria 2. Severe anaemia (haemoglobin 3. Known hypersensitivity to the IMP or any of the excipients or to medicinal products with similar chemical structures (i.e. heparin or LMWHs) 4. History of significant bleeding (e.g. upper GI bleeding, recurrent epistaxis, joint bleeding, melena) 5. History of heparin induced thrombocytopenia (HIT) 6. Any known severe or debilitating chronic disease 7. History of splenectomy 8. For females: pregnancy, lactating or intention of becoming pregnant within the expected duration of the study (28 days) 9. Thrombocytopenia 10. Liver function tests (ASAT/ALAT levels) more than 2.5 times the upper limit of normal range 11. Documented adequate parenteral antimalarial treatment for >= 24 hours prior to admission 12. Patients with known human immunodeficiency virus (HIV) infection 13. Participation in another clinical trial within 30 days 14. An APTT value >1.5 x ULN 15. Current long-term treatment with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 16. Use of any of the following medications within the past 1 week: Aspirin, Clopidogrel, Dipyridamole or Warfarin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective is to evaluate the safety and tolerability of sevuparin/DF02 when administered IV every 6 hours until patient recovery or until start of oral medication for a maximum of 3 consecutive days (minimum 5 doses) as adjunctive therapy to IV artesunate in patients with moderate to severe P. falciparum malaria. Safety and tolerability will be assessed by observing occurrence and frequency of relevant adverse eventsTimepoint: The primary outcome will be measured in each study visit as follows : Day 1 Day 2 Day 3 Daily until discharge Day 7 Day 14 Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Improvement of retinopathy as assessed by retinal photographyTimepoint: (It at 0, 6, and 24 h after enrolment for all study patients and for those with changes, thereafter daily during the admission and at Day 7, 14 and 28 until full resolution of retinal signs);Mortality rateTimepoint: (Form Day 1 till Day 28);Neurological sequelae as measured by clinical evaluationTimepoint: (Evaluations of neurological sequelae will be performed at discharge for all patients and for those with sequelae also at the follow-up visits (Days 7, 14 and 28) and thereafter at 3, 6 and 12 months after enrolment unless the sequelae resolve earlier.);Normalisation of the plasma Base Excess (BE) as a measure of reversal of metabolic acidosisTimepoint: (At Day 1, Day 2, Day 3 & Daily until discharge);Reversal of hyperlactatemia as a measure of tissue hypoxemiaTimepoint: (Will be measured from venous blood immediately after end of first dose of IMP and then every 6 hours until normalized.);To assess the efficacy of sevuparin/DF02, given as adjunctive therapy on: 1. Dynamics of different developmental stages of malaria parasites in peripheral blood Timepoint: (At screening, before the first dose of IMP, pre-dose and at 1, 2, 4, 5, 7, 9, 12, 15, 18 hours after first dose of study treatment, thereafter every 6 hours until 2 negative slides have been obtained.) ;Coma recovery time in patients with cerebral malaria as measured by the Glasgow Coma Scale (GCS)Timepoint: (Information on the duration of coma prior to admission should be recorded in hours with two decimals (quarter of hours).);Improvement of microcirculatory flow as measured by Orthogonal Polarizing Spectrometry (OPS)Timepoint: (It will be performed immediately before the first dose of study treatment and 6, 24 and 48 hours after the first dose ) | — |
Countries
India
Contacts
Public ContactDr Shariq Anwar
Max Neeman International
Outcome results
None listed