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 Allen Cheng

ORCID ID

Contact details

C/O Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
Bangkok
10400
Thailand
+66 (0)2 3549172
allencheng@ozemail.com.au

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

ACTRN12605000024640; 077166

Study information

Scientific title

Granulocyte colony-stimulating factor in ceftazidime-treated patients in septic shock due to melioidosis: a placebo-controlled double-blind prospective randomised trial

Acronym

Study hypothesis

In Darwin, Australia, the mortality in patients with melioidosis with septic shock has fallen from 95% (20 of 21 patients) to 10% (2 of 21 patients) since the adoption of granulocyte colony-stimulating factor (G-CSF). The hypothesis tested by this prospective randomised trial is that G-CSF can reduce the mortality of melioidosis-associated severe sepsis.

Ethics approval

1. The Ministry of Public Health, Royal Government of Thailand
2. The Human Research Ethics Committee of the Menzies School of Health Research, Australia

Study design

Double-blind, prospective, randomised trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Condition

Septic shock due to melioidosis

Intervention

Patients will be treated with ceftazidime (the antibiotic treatment of choice), and randomised to receive either placebo or Lenograstim (recombinant human granulocyte colony stimulating factor [rhG-CSF]) (Granocyte®-Chugai Pharmaceutical, Japan). Dose: 300 µg intravenous injection, once daily for three days.

Intervention type

Drug

Phase

Not Applicable

Drug names

Ceftazidime, lenograstim

Primary outcome measures

The primary outcome measures will be in-hospital mortality and 28 day mortality.

Secondary outcome measures

Secondary outcome measures will include the following:
1. Treatment failure: unfavourable outcome or changing the regimen using these criteria:
1.1. Obvious worsening of clinical signs and symptoms after 72 hours of treatment such as lowering of blood pressure, deterioration of shock
1.2. B. pseudomallei persistently cultured in blood after seven days of treatment
1.3. Persistent fever and no obvious improvement in any clinical signs and symptoms after ten days of treatment in the presence of other proper management such as surgical drainage of pus or fluid collection
2. Fever clearance time
3. Adverse drug reactions
4. Sequential Organ Failure Assessment (SOFA) scores at day one, three, seven and ten
5. Time to resolution of shock
6. Duration of ventilation
7. Duration of hospitalisation
8. Neutrophil function before and after treatment

Overall trial start date

01/06/2003

Overall trial end date

01/11/2005

Reason abandoned

Eligibility

Participant inclusion criteria

1. Community acquired septic shock (must fulfil criteria for sepsis, shock and end-organ perfusion abnormalities), and melioidosis is suspected:
1.1. Sepsis: Systemic Inflammatory Response Syndrome (SIRS): two or more of the following, clinically ascribed to infection:
1.1.1. Fever: temperature more than 38°C or less than 36°C
1.1.2. Tachycardia: heart rate more than 90 beats/min
1.1.3. Tachypnoea: respiratory rate more than 20 breaths/min or arterial carbon dioxide pressure (PaCO2) less than 32 mmHg or mechanical ventilation
1.1.4. White cell count more than 12,000 cells/ml or less than 4,000 cells/ml or more than 10% band forms
1.2. Shock: hypotension for more than one hour in absence of other causes of hypotension (e.g. anaesthesia or antihypertensive medication) despite adequate fluid challenge sufficient to restore circulating blood volume (systolic blood pressure less than 90 mmHg or fall of more than 40 mmHg from baseline or requirement for vasopressors/inotropes)
1.3. Septic shock: sepsis with shock with markers of perfusion abnormalities that may include one or more of:
1.3.1. Metabolic acidosis: pH less than 7.3 or base excess less than 5 or bicarbonate (HCO3) less than 15 mmol/l or anion gap more than 20 mmol/l or lactate more than 4 mg/l
1.3.2. Respiratory dysfunction: mechanical ventilation or partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) less than 300 or respiratory rate less than 5 or more than 49 breaths/min or PaCO2 more than 50 mmHg or PaO2/partial pressure of oxygen in the alveoli (PAO2) ratio less than 0.5
1.3.3. Renal dysfunction: oliguria less than 30 ml/hour for three hours, or oliguria less than 700 ml/24 hours or creatinine more than 3 mg/dl or renal replacement therapy
1.3.4. Altered mental status Glasgow Coma Score (GCS) less than 15
1.3.5. Liver dysfunction: bilirubin more than 6 mg/dl and prothrombin time (PT) more than four seconds above normal control
1.3.6. Coagulopathy: International Normalised Ratio (INR) more than 1.4
2. Community acquired septicaemia (less than 72 hours of hospitalisation)
3. Patients who have received antibiotics prior to presentation are eligible
4. No known hypersensitivity to G-CSF
5. Aged more than 14 years, either sex
6. Need hospitalisation and intravenous antibiotic administration
7. Willingness to participate in the study and written, informed consent obtained from the patient

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

1. Known haematological malignancy, myelodysplasia or congenital neutropaenia
2. Febrile neutropaenia
3. Pregnant or lactating women
4. Known hypersensitivity to G-CSF
5. Patients not expected to remain in hospital for treatment
6. Known objection to participation in study
7. Patients who have previously been enrolled or who have received G-CSF within the past month
8. Patients with community-acquired sepsis with cultures positive for other organisms

Recruitment start date

01/06/2003

Recruitment end date

01/11/2005

Locations

Countries of recruitment

Thailand

Trial participating centre

C/O 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.jr2.ox.ac.uk/ndm/Tropical_Medicine

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

2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17599307

Publication citations

  1. Results

    Cheng AC, Limmathurotsakul D, Chierakul W, Getchalarat N, Wuthiekanun V, Stephens DP, Day NP, White NJ, Chaowagul W, Currie BJ, Peacock SJ, A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand., Clin. Infect. Dis., 2007, 45, 3, 308-314, doi: 10.1086/519261.

Additional files

Editorial Notes