Tigecycline in the empiric therapy of fever in high-risk granulocytopenic haematologic cancer patients
| ISRCTN | ISRCTN00586497 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN00586497 |
| EudraCT/CTIS number | 2006-006210-14 |
| Secondary identifying numbers | N/A |
- Submission date
- 18/06/2012
- Registration date
- 17/07/2012
- Last edited
- 06/10/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Cancer patients undergoing intensive chemotherapy can become granulocytopenic (low level of white blood cells), leaving them at high risk of developing infections, which may be lethal if antibiotic treatment is not promptly started. Currently, treatment with a single antibiotic is the standard treatment, but this approach may be inadequate due to the increasing number of infections caused by multi-drug resistant bacteria. To investigate the possible benefits of more aggressive antibiotic treatment, the aim of this study is compare the effectiveness of the antibiotic combination piperacillin-tazobactam with or without Tigecyclin, a new broad-spectrum antibiotic.
Who can participate?
Cancer patients, aged over 18, with fever and chemotherapy-induced neutropenia (low level of white blood cells)
What does the study involve?
Participants are randomly allocated to receive either piperacillin-tazobactam or piperacillin-tazobactam plus tigecycline. At the end of the study the success rates of the two treatments are compared. The response is considered a success if fever and clinical signs of infection are resolved and if the infecting microorganisms are eradicated without changing the allocated treatment. Patient survival is also assessed after 30 days.
What are the possible benefits and risks of participating?
The study's results may help to find the best way to treat bacterial infections in high-risk cancer patients. The main risk is the possible increased side effects with the combined antibiotic treatment. Therefore, participants are strictly monitored for the occurrence of side effects.
Where is the study run from?
28 cancer centres in Italy
When is the study starting and how long is it expected to run for?
May 2008 to November 2010
Who is funding the study?
University of Perugia (Italy)
Who is the main contact?
Dr Giampaolo Bucaneve
clime@unipg.it
Contact information
Scientific
Istituto di Medicina Interna e Scienze Oncologiche
Azienda Ospedale Università
Ospedale S. Maria della Misericordia
S. Andrea delle Fratte
Perugia
06156
Italy
| Phone | +39 (0)755 784493 |
|---|---|
| clime@unipg.it |
Study information
| Study design | Prospective multicentre randomized controlled unblinded clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please contact Dr Giampaolo Bucaneve, farmacli@unipg.it to request a patient information sheet |
| Scientific title | Prospective, randomised, multicentre controlled trial on empiric antibiotic therapy in febrile neutropenic cancer patients: piperacillin and tazobactam plus tigecycline versus piperacillin or tazobactam monotherapy |
| Study objectives | A more aggressive antibacterial approach with a combination regimen including Tigecycline, a new broad spectrum antibiotic, may be more effective than monotherapy. Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic cancer patients, but this approach may be inadequate due to the increasing prevalence of infections caused by multidrug resistant bacteria. |
| Ethics approval(s) | Hospitals of Umbria Ethics Committee (Comitato Etico delle Aziende Sanitarie della Regione Umbria), 14/12/2006, ref: 13846/07/ACC |
| Health condition(s) or problem(s) studied | Febrile neutropenia/bacterial infections in immunocompromised cancer patients |
| Intervention | Patients were randomized to receive intravenous piperacillin-tazobactam or intravenous piperacillin-tazobactam plus tigecycline.187 were assigned to receive intravenous piperacillin-tazobactam and 203 to receive intravenous piperacillin-tazobactam plus tigecycline. Over a period of two years, at each participating centers, febrile neutropenic cancer patients were assigned to receive an antibiotic monotherapy (piperacillin-tazobactam, 4.5 g intravenously every 8 hours) or a combination regimen (piperacillin-tazobactam, 4.5 g intravenously every 8 hours, plus tigecycline, 50 mg intravenously every 12 hours). The maximum duration of the treatment was 14 days. At the end of the study we compared the success- rates of the two groups of treatment. We considered the response a success if fever and clinical signs of infection resolved and if the infecting microorganisms were eradicated without change of the initial allocated therapy. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Piperacillin, tazobactam, tigecycline |
| Primary outcome measure | The success rates of the antibiotic regimens. We considered the response a success if fever and clinical signs of infection resolved and if the infecting microorganisms were eradicated without change of the initial allocated treatment. Response was defined as a failure if the patient died as a result of primary infection; if bacteremia persisted beyond the first 24 hours of therapy; if a breakthrough bacteremia was documented; if the isolated pathogen was resistant to the assigned antibiotics; if no response was seen after at least 72 hours of empiric therapy; if shock or acute respiratory distress syndrome or a disseminated intravascular coagulation or multiple organ failure was observed; if infection relapsed within 7 days of discontinuation of treatment; and if toxicity occurred that required interruption of treatment. Response was also evaluated by assessing survival at day 30. |
| Secondary outcome measures | Safety and tolerability of the two antibiotic regimens |
| Overall study start date | 03/05/2008 |
| Completion date | 04/11/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | A total of 390 febrile neutropenic cancer patients were enrolled |
| Key inclusion criteria | 1. Consecutive adult (>18 age) 2. Cancer patients were eligible for randomization if they had fever ((≥38.5°C on one occasion or ≥38°C on two or more occasions within 12 hours) 3. Chemotherapy-induced neutropenia (absolute neutrophils count less than 1000 per cubic millimeter anticipated to decrease to fewer than 500 cells per cubic millimeter within 24 to 48 hours) and a presumed infection 4. Patients were enrolled only once in the study and were hospitalized at the participating centres |
| Key exclusion criteria | 1. Had received any intravenous antibiotics during the preceding 96 hours 2. Had a known allergy to any of the protocol antibiotics 3. Had renal failure requiring hemo- or peritoneal dialysis or a serum creatinine level greater than 25 ml/min 4. Were pregnant or had known human immunodeficiency virus infection |
| Date of first enrolment | 03/05/2008 |
| Date of final enrolment | 04/11/2010 |
Locations
Countries of recruitment
- Italy
Study participating centre
06156
Italy
Sponsor information
University/education
[Università degli studi di Perugia]
Dipartimento di Medicina Clinica e Sperimentale
Azienda Ospedale Università
S. Andrea delle Fratte
Perugia
06156
Italy
| Phone | +39 (0)755 783436 |
|---|---|
| misoseg@unipg.it | |
| Website | http://www.unipg.it |
"ROR" |
https://ror.org/00x27da85 |
Funders
Funder type
University/education
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 |
Editorial Notes
06/10/2016: Plain English summary added.
