To evaluate the preliminary efficacy and feasibility of interferon gamma as adjunctive treatment in combination with the standard regimen, for the treatment of patients with candidemia using the following parametersSecondary objective: to evaluate…
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
- Fungal infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the time to negative blood cultures.
Secondary outcome
Secondary endpoints are
• The overall survival
• Mortality at week 2 and week 8 after end of treatment (all causes)
• Time to death
• Outcome of fungal infection:
o Resolution of infection at week 2 and 8 after end of treatment
o Evaluation of patient status (succes, failure, death) at end of interferon
gamma (and at time of stopping antifungal treatment)
o Microbiological evaluation
• Duration of antifungal treatment
• Duration of hospitalization
• Immunological parameters
• Evaluation of host respons markers that can be used to identify patients with
immunoparalysis that will benefit from immunotherapy
• Monitoring the immunological respons to interferon-gamma
Background summary
Over the past decade, systemic infections caused by fungal pathogens, and
particularly by Candida species, have become a prominent cause of disease,
especially in severely ill immunocompetent and immunocompromised patients.
Advances in health care technology and life support systems have increased the
risk of nosocomial Candida infection.
The mortality rate associated with candidemia, independent of death from the
underlying disease, is high at around 40%, and tends to increase in patients
with unremitting underlying disease. The extent of the alteration of the host
defense rather than pathogenic properties of the fungus appear to be the most
important determinants of the severity of disease. *Most likely, sepsis-induced
immunoparalysis in patients admitted to an intensive care unit (ICU) is an
important factor leading to weakened host defenses and increased susceptibility
to invasive candidiasis.
The host response to C. albicans infection is a complex interplay between
cellular and humoral immunity and usually provides a sufficient defense against
the microorganism in the healthy host. Interferon(IFN)-gamma is a key cytokine
for innate as well as acquired resistance to candidiasis. Thus, in view of the
relative deficiency of IFN-gamma in candidemic patients - especially those with
sepsis-induced immunoparalysis - and the beneficial effects of IFN-gamma on
anti-Candida host defense mechanisms, suppletion of rIFN-gamma is rational as
adjunctive therapy in patients with severe invasive candidasis or candidemia,
in addition to treatment with conventional antifungal drugs.
Study objective
To evaluate the preliminary efficacy and feasibility of interferon gamma as
adjunctive treatment in combination with the standard regimen, for the
treatment of patients with candidemia using the following parameters
Secondary objective: to evaluate host response markers that could be used to
identify the patients who will benefit from immunotherapy according to their
immunological status, and to monitor the patient*s immunological response to
IFN-gamma.
Study design
Multicentre randomized open label study
Intervention
The intervention study group will receive 100 mcg of Interferon gamma through
subcutaneous injection, thrice weekly during two weeks. The control group will
receive no Interferon gamma.
Study burden and risks
Patients with candidemia are already admitted to a hospital. Therefore patients
will not have to invest extra time in for the sake of study visits during their
treatment. Daily sampling of blood for clinical purposes is standard care.
Bloodsampling for this study will be combined with already planned
venipunctures. Bloddcultures and biochemistry are performed as standard care in
candidemic patients. Furthermore an extra amount of 22.5 ml of blood will be
drawn 5 times during the first week, one time in the second week and at 2 and 8
weeks after the end of therapy.
Study treatment consists of in total 6 subcutaneous injections that will be
given thrice weekly during 2 weeks. Besides local pain at the site of
injection, interferon can cause (mild) flu-like reactions
De interventie bestaat uit 6 subcutane injecties die gedurende 2 weken, drie
maal per week worden toegediend. Naast locale pijn op de injectieplaats kan
interferon-gamma leiden tot (milde) griepachtige verschijselen, die in het
algemeen met eventueel paracetamol goed verdragen worden.
Candidemie is een ernstige infectie met een zeer hoge mortaliteit. De
bijwerkingen zijn in het algemeen zodanig mild dat deze niet opwegen tegen de
potentiele voordelen van een verbetering van de immuunrespons tegen deze
infectie. Het middel is dan ook reeds geregistreerd in selecte
patientenpopulaties (verlagen van de frequentie van ernstige infecties zoals
Candida bij chronisch granulomateuze ziekte en maligne osteopetrosis)
Postbus 9101
6500HB Nijmegen
NL
Postbus 9101
6500HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
• Males or non-pregnant females (who must agree to use barrier methods of contraception during the study therapy period, women of childbearing age must have a negative urine pregnancy or serum test at baseline).
• Subjects who are 18 years of age or older
• Subjects with at least one positive blood culture isolation of Candida species from a specimen drawn within 96 hours prior to study entry.
• Subjects who have clinical evidence of infection AT SOME TIME WITHIN 96 HOURS PRIOR TO ENROLLMENT, including AT LEAST ONE of the following:
-Temperature >37.8 *C on 2 occasions at least 4 hours apart or one measurement > 38.2 *C
-Systolic blood pressure <90 or a >30 mmHg decrease in systolic BP from the subject*s normal baseline.
-Signs of inflammation (swelling, heat, erythema, purulent drainage) from a site infected with Candida (eg, joint, skin, eye, bone, esophagus)
-Radiologic findings of invasive canidiasis
•Subject or their legal representative must sign a written informed consent form.
Exclusion criteria
• Subjects with a history of allergy or intolerance to echinocandins or Interferon gamma
• Subjects with an absolute neutrophil count of less than 500/mm3 at study entry
• Women who are pregnant or lactating
• Subjects who are unlikely to survive more than 24 hours
• Subjects who have failed previous systemic antifungal therapy for the Candida spp. infection which is being studied.
• Subjects who have received more than 48 hours of systemic antifungal therapy for the current episode, within 96 hours prior to study entry.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014600-66-NL |
| CCMO | NL28823.091.10 |
| Other | volgt |