search  
 


Home

Who are we?

Why
register?


Signup for
registration


Online registration

Log in to register
your trial


Search a trial

NRT en CCMO

Contact

NEDERLANDS





MetaRegister
van CCT (UK)


ISRCTN-Register
van CCT (UK)


Short vs. long treatment with imipenem for unexplained fever during neutropenia in hematology patients receiving antimicrobial prophylaxis: A randomized non-inferiority trial.


- candidate number13467
- NTR NumberNTR3675
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR22-okt-2012
- Secondary IDs80-83600-98-10158 ZonMw
- Public TitleShort vs. long treatment with imipenem for unexplained fever during neutropenia in hematology patients receiving antimicrobial prophylaxis: A randomized non-inferiority trial.
- Scientific TitleEarly discontinuation vs. extended treatment with imipenem for unexplained fever during neutropenia in hematology patients receiving antimicrobial prophylaxis: A randomized non-inferiority trial.
- ACRONYM
- hypothesisEarly discontinuation of empirical treatment with imipenem in hematology patients with unexplained fever during neutropenia is non-inferior to extended treatment with imipenem with regard to treatment success.
- Healt Condition(s) or Problem(s) studiedHematological malignancy, Neutropenia, Fever, Chemotherapy, Stem cell transplantation
- Inclusion criteria1. Patients with hematological diseases being treated with cytotoxic chemotherapy or stem cell transplantation;
2. Expected duration of neutropenia (neutrophil count <0.5*10^9/l) of >7 days;
3. Fever (axillary temperature>38.5C for at least 2 hours) of undetermined origin;
4. Age 18 years or older;
5. Written informed consent.
- Exclusion criteria1. Contraindication to use of imipenem-cilastatin;
2. Prednisone use >=10 mg/day;
3. A clinically or microbiologically documented infection (defined as a clinical assessment that infection is present judged on findings from physical assessment, patient history or imaging; or a positive culture from blood, urine, sputum, broncho-alveolar lavage or any other material normally sterile);
4. Symptoms of septic shock (systolic blood pressure <90mm Hg unresponsive to fluid rescuscitation and/or oliguria);
5. Any patient who already participated in this trial during an earlier neutropenic fever episode.
- mec approval receivedno
- multicenter trialyes
- randomisedyes
- masking/blindingSingle
- controlActive
- groupParallel
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 1-jan-2013
- planned closingdate1-jan-2016
- Target number of participants224
- InterventionsTREATMENT:
At the onset of fever, all eligible patients will receive the standard care for neutropenic fever:
1. Full diagnostic work-up including physical examination, two blood cultures (from which 1 from a central venous catheter if present), chest X-ray and additional diagnostic procedures (imaging, cultures, etc.) depending on clinical signs;
2. Treatment is started with imipenem-cilastatin 500mg QID (referred to as imipenem).

INFORMED CONSENT AND RANDOMISATION:
Within 48hours after onset of fever every eligible patient will be asked for informed consent. Each consenting patient is then randomized to either the early discontinuation arm or the extended treatment arm. This is the start of the treatment protocol.

EARLY DISCONTINUATION ARM:
After 4*24 hours after onset of fever, imipenem will be discontinued and patient will be evaluated. If fever has resolved, no further action will be undertaken. If fever persists antifungal treatment with voriconazole is started (or anidulafungin in case of azole-resistant fungi in surveillance cultures) and is continued until either defervescence or resolve of neutropenia (neutrophil count >0.5*10^9/l) occurs.

EXTENDED TREATMENT ARM:
After 4*24 hours after onset of fever, presence of fever will be determined. If no fever is present, imipenem is continued for 5 more days to be discontinued after a total of 9 days. If fever persists, antifungal treatment with voriconazole is started (or anidulafungin in case of azole resistant fungi in surveillance cultures) and imipenem is continued for more than 5 days and is continued until either defervescence or resolve of neutropenia (neutrophil count >0.5*10^9/l) occurs.
- Primary outcomeWe will compare the treatment arms on the primary outcome treatment success at the end of protocol. Treatment is defined as unsuccessful if the patient:
1. Has fever (axillary temperature>38.5C for at least 2 hours) at the first day of the end of the neutropenic episode (defined as the first day with neutrophil count >0.5*10^9/l);
2. Has experienced recurrence of fever (recurrence of axillary temperature>38.5C for at least 2 hours after >24h defervescence) after start of the treatment protocol;
3. Is diagnosed with a clinically or microbiologically documented infection after start of treatment protocol;
4. Shows signs or symptoms of septic shock (systolic blood pressure <90mm Hg unresponsive to fluid rescuscitation and/or oliguria) after start of treatment protocol;
5. Dies after start of treatment protocol.
- Secondary outcomeWe will also compare the treatment arms on the following secondary outcomes:
1. 60-day infection-related mortality, starting at day 1 of chemotherapy or stem-cell therapy induction;
2. 60-day all-cause mortality, starting at day 1 of chemotherapy or stem-cell therapy induction;
3. incidence of serious adverse effects and toxicity;
4. incidence and prevalence of liver- and kidney dysfunction;
5. Candida spp. colonisation in (surveillance) cultures;
6. Resistant bacteria in (surveillance)-cultures;
7. Cost of antimicrobial therapy per admission;
8. Length of hospital stay;
9. Time to defervescence (disappearance of fever).
- TimepointsThe study protocol will end after any of the following events:
1. Diagnosis of a clinically or microbiologically documented (a clinically documented infection is defined as a clinical assessment that infection is present judged on findings from physical assessment, patient history or imaging; a microbiologically documented infection is defined as: positive culture from blood, urine, sputum, broncho-alveolar lavage or any other material normally sterile);
2. In case the patient shows symptoms of septic shock (systolic blood pressure <90mm Hg unresponsive to fluid rescuscitation and/or oliguria);
3. End of the neutropenic episode (neutrophil count <0.5*10^9/l);
4. Death due to any cause;
5. Lack of patient compliance (especially refusal to continue treatment according to protocol);
6. Major protocol violation;
7. Contra-indication to administer imipenem due to allergy or side effects;
8. Recurrence of fever (recurrence of axillary temperature>38.5C for at least 2 hours after >24h defervescence) after start of the treatment protocol.
- Trial web sitewww.vumc.nl
- statusplanned
- CONTACT FOR PUBLIC QUERIESDhr. J.J. Sikkens
- CONTACT for SCIENTIFIC QUERIESDhr. J.J. Sikkens
- Sponsor/Initiator VU University Medical Center
- Funding
(Source(s) of Monetary or Material Support)
- PublicationsN/A
- Brief summaryRandomized clinical trial aimed at investigating whether the duration of empiric antibacterial therapy in patients with hematologic malignancies and unexplained neutropenic fever can be safely reduced. A multi-center randomized clinical non-inferiority trial comparing safety of early discontinuation (4 days) vs extended treatment (9 or more days) with imipenem-cilastatin for hematology patients with unexplained fever during iatrogenic neutropenia is proposed.
- Main changes (audit trail)
- RECORD22-okt-2012 - 19-nov-2012


  • Indien u gegevens wilt toevoegen of veranderen, kunt u een mail sturen naar nederlands@trialregister.nl