A placebo-controlled trial of granulocyte colony-stimulating factor in ceftazidime-treated patients in septic shock due to melioidosis
| ISRCTN | ISRCTN26167403 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN26167403 |
| Secondary identifying numbers | ACTRN12605000024640; 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 Allen Cheng
Scientific
Scientific
C/O Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
Bangkok
10400
Thailand
| Phone | +66 (0)2 3549172 |
|---|---|
| allencheng@ozemail.com.au |
Study information
| Study design | Double-blind, prospective, randomised trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Scientific title | Granulocyte colony-stimulating factor in ceftazidime-treated patients in septic shock due to melioidosis: a placebo-controlled double-blind prospective randomised trial |
| Study objectives | 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(s) | 1. The Ministry of Public Health, Royal Government of Thailand 2. The Human Research Ethics Committee of the Menzies School of Health Research, Australia |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Ceftazidime, lenograstim |
| Primary outcome measure | 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 study start date | 01/06/2003 |
| Completion date | 01/11/2005 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 60 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/06/2003 |
| Date of final enrolment | 01/11/2005 |
Locations
Countries of recruitment
- Thailand
Study participating centre
C/O Wellcome Unit
Bangkok
10400
Thailand
10400
Thailand
Sponsor information
University of Oxford (UK)
University/education
University/education
CCVTM
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
England
United Kingdom
| Phone | +44 (0)1865 857433 |
|---|---|
| ccvtm@clinical-medicine.oxford.ac.uk | |
| Website | http://www.jr2.ox.ac.uk/ndm/Tropical_Medicine |
"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 | 01/08/2007 | Yes | No |
