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11 February 2012
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| [ Print-friendly version ] |
| N-AcetylCysteine as anti-oxidative treatment in severe malaria |
| ISRCTN | ISRCTN20156397 |
| ClinicalTrials.gov identifier | |
| Public title | N-AcetylCysteine as anti-oxidative treatment in severe malaria |
| Scientific title | A randomised, double-blind, placebo-controlled trial of N-AcetylCysteine as adjunctive therapy in the treatment of severe falciparum malaria |
| Acronym | NAC Study |
| Serial number at source | 077166 |
| Study hypothesis | A previous pilot study in Thailand in patients with severe malaria suggested that N-acetylcysteine (NAC) shortened the time to normalisation of plasma lactate and Glasgow Coma Score, both well established markers of disease severity and prognosis. NAC is an antioxidant drug widely used in the treatment of paracetamol poisoning and is being investigated for beneficial effects in a diverse range of diseases. It is very safe. We propose to extend the malaria pilot study to a larger randomised, double-blind, placebo-controlled trial of N-acetylcysteine as adjunctive therapy in the treatment of severe falciparum malaria. |
| Lay summary | |
| Ethics approval | Not provided at time of registration |
| Study design | Randomised controlled trial |
| Countries of recruitment | Thailand |
| Disease/condition/study domain | Falciparum malaria |
| Participants - inclusion criteria |
Adults patients (more than or equal to 16 years old, either sex) with a diagnosis of severe malaria: asexual Plasmodium falciparum parasitaemia with one or more of the following criteria:
1. Glasgow coma scale less than 11 2. Haematocrit less than 20% with parasite count more than 100,000/mm^3 3. Jaundice with bilirubin more than 2.5 mg/dl with parasite count more than 100,000/mm^3 4. Serum creatinine more than 3 mg/dl with urine less than 400 ml/24 hours 5. Hypoglycaemia with venous glucose more than 40 mg/dl 6. Systolic blood pressure less than 80 mmHg with cool extremeties 7. Peripheral asexual stage parasitaemia more than 10% 8. Peripheral venous lactate more than 4 mmol/l 9. Peripheral venous bicarbonate less than 15 mmol/l |
| Participants - exclusion criteria |
1. Inability or unwillingness to give informed consent by patient or attendant relatives
2. Pregnancy or breast feeding. A pregnancy test will be performed on indication 3. Known hypersensitivity to NAC 4. History of asthma or wheeze detected on auscultation on admission 5. Previous treatment with lactate containing intravenous fluid (e.g. Ringer’s Lactate Solution) |
| Anticipated start date | 01/06/2004 |
| Anticipated end date | 31/12/2007 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 100 - recuitment ends 1st October 2006 |
| Interventions |
This will be a randomised, double-blind, placebo-controlled trial of the efficacy and safety of N-acetylcysteine in the adjunctive treatment of severe falciparum malaria, enrolling 100 patients.
Antimalarial and supportive treatment will be in accordance with international (World Health Organisation [WHO] 2000) and local hospital guidelines. Antimalarial drug treatment will be with intravenous artesunate (2.4 mg/kg body weight stat followed by 2.4 mg/kg at 12 hours and 24 hours and then every 24 hours) and, when able to take oral medication, artesunate (50 mg) tablets to give a total artesunate dose of 12 mg/kg over a total of seven days. NAC will be given in the standard regime used in the treatment of paracetamol toxicity: 1. 150 mg/kg in 200 ml 5% dextrose water (5% DW)/15 min 2. Then 50 mg/kg in 500 ml 5% DW/4 hours 3. Then 100 mg/kg in 1000 ml 5% DW/16 hours The anticipated end date of this trial has been extended to the end of 2007. The previous end date was 1st October 2006. |
| Primary outcome measure(s) |
1. Serial plasma lactate, glucose, serum creatinine, bilirubin and acid-base status
2. Serial Glasgow Coma Score (GCS) and vital signs 3. Parasite clearance time 4. Adverse events |
| Secondary outcome measure(s) |
1. Serial red cell deformability
2. Serial observation of the microcirculation on the mucosal surface using a non-invasive method, Orthogonal Polarising Spectrometry (Groner et al, 1999) 3. Serial plasma cytokine (Interleukin [IL]-6, 8, 10 and Tumour Necrotising Factor [TNF]) concentrations and measures of oxidative stress (F2-isoprostanes) 4. Mortality |
| Sources of funding | The Wellcome Trust (UK) (grant ref: 077166) |
| Trial website | |
| Publications | 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19114891 |
| Contact name | Dr Arjen Dondorp |
| Address |
Wellcome Unit
Faculty of Tropical Medicine 420/6 Rajvithi Road |
| City/town | Bangkok |
| Zip/Postcode | 10400 |
| Country | Thailand |
| Tel | +66 (0)2 3549172 |
| Fax | +66 (0)2 3549169 |
| arjen@tropmedres.ac | |
| Sponsor | University of Oxford (UK) |
| Address |
CCVTM
Churchill Hospital Old Road Headington |
| City/town | Oxford |
| Zip/Postcode | OX3 7LJ |
| Country | United Kingdom |
| Tel | +44 (0)1865 857433 |
| Fax | +44 (0)1865 857407 |
| ccvtm@clinical-medicine.oxford.ac.uk | |
| Sponsor website: | http://www.ox.ac.uk/ |
| Date applied | 12/09/2005 |
| Last edited | 06/02/2009 |
| Date ISRCTN assigned | 14/10/2005 |
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| © 2012 ISRCTN unless otherwise stated. | |
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