Condition category
Infections and Infestations
Date applied
12/09/2005
Date assigned
14/10/2005
Last edited
21/03/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Arjen Dondorp

ORCID ID

Contact details

Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
Bangkok
10400
Thailand
+66 (0)2 3549172
arjen@tropmedres.ac

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

077166

Study information

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

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.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Condition

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

Phase

Not Applicable

Drug names

N-acetylcysteine

Primary outcome measures

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 trial start date

01/06/2004

Overall trial end date

31/12/2007

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

100 - recuitment ends 1st October 2006

Participant 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)

Recruitment start date

01/06/2004

Recruitment end date

31/12/2007

Locations

Countries of recruitment

Thailand

Trial participating centre

Wellcome Unit
Bangkok
10400
Thailand

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

CCVTM
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom
+44 (0)1865 857433
ccvtm@clinical-medicine.oxford.ac.uk

Sponsor type

University/education

Website

http://www.ox.ac.uk/

Funders

Funder type

Charity

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19114891

Publication citations

  1. Results

    Charunwatthana P, Abul Faiz M, Ruangveerayut R, Maude RJ, Rahman MR, Roberts LJ, Moore K, Bin Yunus E, Hoque MG, Hasan MU, Lee SJ, Pukrittayakamee S, Newton PN, White NJ, Day NP, Dondorp AM, N-acetylcysteine as adjunctive treatment in severe malaria: a randomized, double-blinded placebo-controlled clinical trial., Crit. Care Med., 2009, 37, 2, 516-522, doi: 10.1097/CCM.0b013e3181958dfd.

Additional files

Editorial Notes