reactivation of cytomegalovirus infection
Conditions
Interventions
Trade Name: valtrex (valaciclovir)
Product Name: valaciclovir
Pharmaceutical Form: Tablet
INN or Proposed INN: valaciclovir
CAS Number: 124832-26-4
Concentration unit: g gram(s)
Concentration type: eq
Sponsors
University Hospitals Birmingham NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Total hospital stay of less than 7 days •This study aims to assess prophylaxis to prevent CMV reactivation. Patients screened for inclusion will include those hospitalised for less than 7 days prior to admission to intensive care in order to minimise the inclusion of patients admitted late on in their disease process, with pre-existing critical illness CMV reactivation. Inpatients deemed medically fit in the 7 days prior to ICU admission, eg rehab wards will be accepted for study inclusion CMV seropositive •Patients testing CMV positive only will be approached for inclusion in the interventional arm of the study. Patients testing CMV negative will enter the observational arm of the study, and no patient identifiers will be retained. ICU stay of >48 hours •Patient recruitment will be deferred until the end of a 24hr period on the ICU. This period is essential in order to develop a rapport with the patient and family as part of the consent process, to obtain results of CMV status assays, and to make an assessment regarding suitability of the patient for inclusion in the study. Mechanically ventilated, anticipated to continue for > 48 hours •In order to minimise the numbers of patients receiving therapy unnecessarily, and maximise the likelihood of identifying a clinical effect, the study group selects patients with higher risk of reactivation based on previous publications. Are the trial subjects under 18? no Number of subjects for this age range: 141 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Age <18 years Pregnancy or breast feeding Expected to survive < 48hrs Confirmed immunosuppression •Known or suspected Human Immunodeficiency Virus infection •Known or suspected underlying immunodeficiency (organ transplant, congenital immunodeficiency, in receipt of immunosuppressive medication e.g. azathioprine, tacrolimus, cyclosporine, sirolimus, cyclophosphamide within 30 days, steroids allowed up to 10mg prednisolone/day on average over 30 days, or stress dose hydrocortisone at up to 400mg/day, short doses of steroids allowed for up to 10 days. •Receipt of chemotherapeutic agent within the last 6 months Severe neutropenia (neutophil count <1000/mm3) Use of systemic antiviral medication within the last 7 days Allergy to study drugs Isolated brain injury
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Does the use of antiviral prophylaxis using valganciclovir or valaciclovir effectively and safely suppress cytomegalovirus reactivation in critically ill patients in intensive care?;Secondary Objective: Critically ill patients are at risk of disease related conditions such as renal failure and bone marrow suppression. Side effects of the antiviral drugs effective against cytomegalovirus may also mimic these conditions. It is likely that some patients will develop these conditions as part of the underlying illness, but be withdrawn from the study drugs as a precaution. We wish to determine whether it is possible to use these antiviral drugs in critically ill patients using a strategy to minimise side effects. We will be recording withdrawals from the trial because of possible side effects, and use this information when designing a large multicentre trial with clinical endpoints.;Primary end point(s): Cytomegalovirus Reactivation as measured by PCR.;Timepoint(s) of evaluation of this end point: evaluated once every 5 days for a total of 28 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Evaluation over 28 days;Secondary end point(s): Secondary Outcomes • CMV PCR secondary outcome measures in blood urine, throat swab or NDBL over 28 day period of data collection o Time to reactivation of CMV PCR defined as above the lower limit of sample assay (blood values used for primary outcome) o time to >1000 and >10000 copies per ml o area under the curve o peak and initial viral load In the event of patient discharge from hospital, death, (or tracheal extubation in the case of NDBL) the results will be censored at the most proximate CMV PCR sample point. • Markers of inflammation o IL6, TNF alpha levels (change between day 0 and day 14/day 28), other herpesviruses (HSV) • Clinical Outcomes o 28 day mortality o Organ Failure free (SOFA<2) days, moderate organ dysfunction (SOFA<5) free days by day 28 o Time to ICU discharge (up to 3 months) o Time to hospital discharge (up to 3 months) Outcome Measures for Safety • Number of serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) • time to neutropenia (count <1.0 x10-9/L) over 28 days • time to thrombocytopenia (plt <50 x10-9/L) over 28 days • Use of GCSF/termination of study drug over 28 days • Number of platelet transfusions over 28 days • time to renal insufficiency (Cr Cl <60ml/min, <30ml/min, need for heamodialysis/haemofiltration) over 28 days | — |
Countries
United Kingdom
Outcome results
None listed