Trial of aciclovir in the prophylaxis of herpes infections in critical care

ISRCTN	ISRCTN29934637
DOI	https://doi.org/10.1186/ISRCTN29934637
Clinical Trials Information System (CTIS)	2006-000612-24
Protocol serial number	WN06AN002
Sponsor	Greater Glasgow Health Board (North Glasgow University Hospitals Division) (UK)
Funder	Chief Scientist Office of the Scottish Executive Health Department (UK) (ref: CZB/4/375)

Submission date: 13/02/2006
Registration date: 14/03/2006
Last edited: 19/05/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Alexander Binning
Scientific

Intensive Therapy Unit
Western Infirmary
Glasgow
G11 5JR
United Kingdom

Study information

Primary study design	Interventional
Study design	Double-blind, randomised, parallel group placebo-controlled trial
Secondary study design	Randomised controlled trial
Scientific title	Trial of aciclovir in the prophylaxis of herpes infections in critical care
Study acronym	TRAPHICC
Study objectives	The overall aim of this proof of concept study is to serve as a pilot study for a multicentre study powered to detect improvement in Intensive Care Unit (ICU) mortality by giving aciclovir prophylaxis to prevent Herpes Simplex Virus (HSV) infection in the lungs. As of 01/06/2009 this record has been updated to include an extension to the anticipated end date; the initial end date at the time of registration was 31/05/2008.
Ethics approval(s)	Multi-Centre Research Ethics Committee for Scotland (Committee A) approved on the 28/03/2008 (ref: 06/MRE00/14; Protocol Number: 3; EudraCT Number: 2006-000612-24).
Health condition(s) or problem(s) studied	Herpes simplex virus infection of the lower respiratory tract in critically ill patients
Intervention	Administration of 15 mg/kg per day aciclovir or placebo by infusion three times daily over 1 hour
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Aciclovir
Primary outcome measure(s)	The primary endpoint is the mean change in Karnofsky index from baseline to day 28 +/- 2 days and 90 +/- 2 days after entry to the study
Key secondary outcome measure(s)	1. Proportion of patients with HSV detected during ICU stay in lower respiratory secretions; proportion of patients with HSV detected during ICU stay in blood samples 2. In patients in whom HSV is detected during ICU stay, proportions of infections due to primary infection and reactivation of latent infection 3. At each sampling time point, the correlation between HSV lymphocyte response and viral titres 4. Mean plasma soluble cytokine levels in patients with and without HSV infection; mean respiratory secretion soluble cytokine levels in patients with and without HSV infection 5. Proportions of patients with HSV reactivation according to type of cytokine response 6. Mean complement activation before HSV is detected, after HSV detection and in patients where HSV is not detected during ICU stay 7. Proportion of patients in whom each of Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Human Herpes Virus Six (HHV6) and Human Herpes Virus Seven (HHV7) infections are detected during ICU stay 8. Median number of days on ventilation, median ICU stay, frequency of prescription of each of anti-retroviral agents, corticosteroids, immunosuppressive agents 9. Proportion of patients surviving at 90 days following ICU admission 10. Number of days of survival following ICU admission 11. The survival time for patients surviving beyond 90 days will be censored at 90 days 12. Proportion of HSV infections which are HSV1, proportion of HSV infections which are HSV2 13. Mean vital signs, white cell count and creatinine clearance during ICU stay 14. Reporting of adverse events occurring during randomised treatment or during the 7 days following the end of randomised treatment
Completion date	30/09/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	500
Key inclusion criteria	1. All patients 18 years or over entering ICU 2. Patient expected to stay in the ICU longer than 36 hours and intubated with an endotracheal or tracheostomy tube within 24 hours of admission to ICU 3. Patient not requiring treatment with aciclovir, valaciclovir, ganciclovir, foscarnet, probenicid or other drug known to have anti-herpes simplex activity 4. Patient must have no known allergy to aciclovir 5. Females of childbearing age must have negative pregnancy test on admission 6. Written informed consent from the patient or assent obtained from relatives
Key exclusion criteria	1. Duration of admission confidently expected to be less than 36 hours 2. Patients with endotracheal or tracheostomy tube placed more than 24 hours before admission to ICU 3. Patient has clinical features of HSV disease 4. Patient previously randomised to this study 5. Patients deemed to be suitable for entry to another trial 6. Previous hypersensitivity to aciclovir or valaciclovir 7. Patient requiring agent with anti-herpes virus activity 8. Patient previously enrolled in another trial of an investigational drug within the past 30 days 9. Patient is pregnant or lactating
Date of first enrolment	01/06/2006
Date of final enrolment	30/09/2009

Locations

Countries of recruitment

United Kingdom
Scotland

Study participating centre

Intensive Therapy Unit

Glasgow
G11 5JR
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results		04/02/2021	19/05/2022	No	No

Editorial Notes

19/05/2022: EU Clinical Trials Register results added.
26/08/2016: No publications found, verifying study status with principal investigator