Cytomegalovirus Control in Critical Care

NCT01503918 | Completed Phase 2 DMC

• 3 other identifiers: RRK41422010-024646-30PB-PG-1010-23225
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether reactivation of latent cytomegalovirus infection in critically ill patients looked after in the intensive care unit can be successfully and safely prevented using antiviral agents. Comparison is made between standard care, and treatment with one of two different antiviral regimens: valaciclovir/aciclovir, which has a favourable side effect profile but requires high dosage to be effective, and valganciclovir/ganciclovir, which has more side effects, but has been demonstrated to be effective in low dosage. The primary hypothesis is that cytomegalovirus reactivation can be effectively suppressed with antiviral prophylaxis.

Conditions

Critical Illness

Keywords

Critical Illness; Critical Care; Valganciclovir; Ganciclovir; Aciclovir; Valaciclovir; Cytomegalovirus

Outcome Measures

Primary Outcomes (1)

• Time to reactivation of cytomegalovirus (CMV) polymerase chain reaction (PCR) (defined as above the lower limit of sample assay).

  In the event of patient discharge from hospital or death, the results will be censored at the most proximate blood CMV PCR sample point.

  28 days

Secondary Outcomes (15)

• Time to reactivation above the lower limit of assay detection of CMV PCR in urine, throat swab and non-directed bronchiolar lavage (NDBL). NDBL whilst trachea is intubated only.

  28 days

• Time to >1000 CMV copies in blood, urine, throat swab and NDBL (NDBL whilst intubated)

  28 days

• Time to >10000 CMV copies in blood, urine, throat swab and NDBL (NDBL whilst intubated)

  28 days

• CMV PCR in blood, urine, throat swab and NDBL (NDBL whilst intubated)

  28 days

• Markers of inflammation

  28 days

Study Arms (3)

Valaciclovir/Aciclovir

EXPERIMENTAL

Drug: Valaciclovir/Aciclovir

Valganciclovir/Ganciclovir

EXPERIMENTAL

Drug: Valganciclovir/Ganciclovir

control

NO INTERVENTION

Interventions

Valaciclovir/Aciclovir DRUG

2g valaciclovir, four times a day, enterally for 28 days, or until discharge from the critical care unit, but for a minimum of 14 days unless discharged from hospital. Those unable to receive enteral drugs will receive intravenous aciclovir 10mg/kg three times a day. Dosing modified in the presence of renal dysfunction.

Valaciclovir/Aciclovir

Valganciclovir/Ganciclovir DRUG

450mg valganciclovir, once a day, by enteral route. Treatment will continue for 28 days, or until discharge from the critical care unit, but for a minimum of 14 days unless discharged from hospital. Intravenous ganciclovir 2.5mg/kg once a day will be used if drugs cannot be given enterally. Treatment dosing will be modified for renal dysfunction

Valganciclovir/Ganciclovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Total hospital stay of less than 7 days
• CMV seropositive
• Critical care stay of \>24 hours
• Mechanically ventilated, anticipated to continue for \> 48 hours

You may not qualify if:

• Known Pregnancy or breast feeding
• Expected to survive less than 48 hours
• Confirmed immunosuppression
• Known or suspected Human Immunodeficiency Virus infection
• Known or suspected underlying immunodeficiency (organ transplantation including stem cell transplantation on immunosuppression, congenital immunodeficiency, in receipt of immunosuppressive medication e.g. azathioprine, methotrexate, tacrolimus, cyclosporine, sirolimus, cyclophosphamide within 30 days)
• Corticosteroids: Prednisolone chronic administration may be used up to a dose of 10mg/day on average over the preceding 30 days, stress dose hydrocortisone (up to 400mg/day) may be used, topical steroids may be used, short duration of higher dose steroids for exacerbations of chronic obstructive pulmonary disease (COPD) up to 1mg/kg prednisolone or equivalent are permitted for up to 14 days
• Receipt of chemotherapeutic agent within the last 6 months
• Use of systemic antiviral medication other than oseltamivir within the last 7 days.
• Intubated and mechanically ventilated secondary to brain injury alone.

Sponsors & Collaborators

• University Hospital Birmingham NHS Foundation Trust: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, West Midlands, B15 2WB, United Kingdom

Location

Related Publications (1)

• Cowley NJ, Owen A, Shiels SC, Millar J, Woolley R, Ives N, Osman H, Moss P, Bion JF. Safety and Efficacy of Antiviral Therapy for Prevention of Cytomegalovirus Reactivation in Immunocompetent Critically Ill Patients: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jun 1;177(6):774-783. doi: 10.1001/jamainternmed.2017.0895.

  PMID: 28437539 DERIVED

MeSH Terms

Conditions

Critical Illness; Multiple Acyl Coenzyme A Dehydrogenase Deficiency

Interventions

Valacyclovir; Acyclovir; Valganciclovir; Ganciclovir

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Julian F Bion, MD FRCP FRCA

  University Hospital Birmingham NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Nicholas J Cowley, MBChB MRCP FRCA

  University Hospital Birmingham NHS Foundation Trust

  STUDY DIRECTOR

• Paul AH Moss, PhD MRCP MRCPath

  University Hospital Birmingham NHS Foundation Trust

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Intensive Care Medicine

Study Record Dates

• First Submitted: December 30, 2011
• First Posted: January 4, 2012
• Study Start: January 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: March 1, 2014
• Last Updated: January 12, 2015

Record last verified: 2015-01

Locations

GB (1)