N-AcetylCysteine as anti-oxidative treatment in severe malaria

ISRCTN	ISRCTN20156397
DOI	https://doi.org/10.1186/ISRCTN20156397
Secondary identifying numbers	077166

Submission date: 12/09/2005
Registration date: 14/10/2005
Last edited: 21/03/2013

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Arjen Dondorp
Scientific

Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
Bangkok
10400
Thailand

Phone	+66 (0)2 3549172
Email	arjen@tropmedres.ac

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Scientific title	A randomised, double-blind, placebo-controlled trial of N-AcetylCysteine as adjunctive therapy in the treatment of severe falciparum malaria
Study acronym	NAC Study
Study objectives	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.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Falciparum malaria
Intervention	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.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	N-acetylcysteine
Primary outcome measure	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 measures	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
Overall study start date	01/06/2004
Completion date	31/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	100 - recuitment ends 1st October 2006
Key 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
Key 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. Ringers Lactate Solution)
Date of first enrolment	01/06/2004
Date of final enrolment	31/12/2007

Locations

Countries of recruitment

Thailand

Study participating centre

Wellcome Unit

Bangkok
10400
Thailand

Sponsor information

University of Oxford (UK)
University/education

CCVTM
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
England
United Kingdom

Phone	+44 (0)1865 857433
Email	ccvtm@clinical-medicine.oxford.ac.uk
Website	http://www.ox.ac.uk/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Charity

The Wellcome Trust (UK) (grant ref: 077166)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2009		Yes	No