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Collaborative H1N1 Adjuvant Treatment pilot trial
ISRCTN ISRCTN45190901
DOI 10.1186/ISRCTN45190901
ClinicalTrials.gov identifier NCT01033955
EudraCT number
Public title Collaborative H1N1 Adjuvant Treatment pilot trial
Scientific title A double-blind placebo-controlled randomised pilot trial of the utility of statins as an adjuvant anti-inflammatory treatment in critically ill adults with suspected, probable or confirmed H1N1
Acronym CHAT
Serial number at source 102785
Study hypothesis Data from both observational studies in humans and interventional studies in animals suggest that the course of influenza can be favourably influenced by agents that are not classically considered to be treatments for influenza. As many of these treatments are inexpensive and readily available, and because they may provide independent benefit in viral infection, they are attractive adjuvant treatments for patients around the world, and ideally suited to use during a global pandemic. Our focus will be on the potential utility of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) as an adjuvant anti-inflammatory treatment in critically ill adults with suspected, probable or confirmed H1N1 based on theoretical potential for benefit and promising experimental studies.
Lay summary
Ethics approval 1. St Michael's Hospital Research Ethics Office approved on the 23rd December 2009 (ref: 09-314)
2. Comite d'ethique de la recherche de l'institut universitaire de cardiologie et de pneumologie de Quebec approved on the 2nd February 2010 (ref: HL-4610)
3. King Abdulaziz University Hospital Biomedical and Research Committee approved 30th January 2010 (ref: 340-10)

All other centres will seek ethics approval before recruiting participants.
Study design Double blind placebo controlled pilot randomised trial
Countries of recruitment Argentina, Australia, Canada, Mexico, New Zealand, Saudi Arabia
Disease/condition/study domain Critically ill influenza A/H1N1 infection
Participants - inclusion criteria 1. Critically ill adult patients greater than 16 years of age (either sex) admitted to an adult intensive care unit (ICU) for any reason with suspected, probable or confirmed novel swine origin influenza A/H1N1 infection
2. Requiring mechanical ventilation (invasive or non-invasive)
3. Receiving antiviral therapy (any medication at any dose and for any intended duration) for less than 72 hours
4. Attending physician or intensivist must have a 'moderate' to 'high' index of suspicion for H1N1
Participants - exclusion criteria 1. Aged less than 16 years
2. Do not resuscitate or re-intubate order documented on chart or anticipated withdrawal of life support
3. Weight less than 40 kg
4. Unable to receive or unlikely to absorb enteral study drug (e.g. incomplete or complete bowel obstruction, intestinal ischaemia, infarction, short bowel syndrome)
5. Rosuvastatin specific exclusions:
5.1. Already receiving a statin (atorvastatin, lovastatin, simvastatin, pravastatin, rosuvastatin)
5.2. Allergy or intolerance to statins
5.3. Receiving niacin, fenofibrate, cyclosporine, gemfibrozil, any protease inhibitor (including but not limited to lopinavir, ritonavir) or planned use of oral contraceptives or estrogen therapy during the Intensive Care Unit (ICU) stay
5.4. Creatine kinase (CK) exceeds 5,000 U/L or alanine aminotransferase (ALT) exceeds 8 times the upper limit of normal (ULN)
6. Severe chronic liver disease (Child-Pugh Score 11 - 15)
7. Previous enrolment in this trial
8. Pregnancy or breast feeding
9. At the time of enrolment, receipt of greater than 72 hours of antiviral therapy
10. Known or suspected clinically significant myositis or myopathy
Anticipated start date 01/01/2010
Anticipated end date 30/08/2011
Status of trial Completed
Patient information material Not available in web format, please use the contact details below to request a patient information sheet
Target number of participants 80
Interventions Please note that as of 29/11/10 the anticpated end date of this study has been extended from 30/08/10 to 30/08/11. This trial is in the recruitment phase.

Experimental drug: Rosuvastatin (Crestor®) -
The first dose of encapsulated study drug (day 1) will be administered within 4 hours of randomisation as a loading dose of 40 mg. Thereafter, doses of 20 mg will be administered daily starting on the next calendar day at 10 pm (+/- 4 hours) as a maintenance dose from days 2 to 14. If the patient is of Asian descent, is aged less than 18 years, or serum creatinine is greater than or equal to 248 µmol/L (2.8 mg/dL) dose adjustments will be made according to a dose adjustment algorithm.

Placebo Comparator -
An identical appearing placebo will be administered to patients in the second study arm and administered once daily through an enteral feeding tube or administered orally if the patient is able to safely take oral medications.

Total duration of treatment: 14 days (both arms)
Total duration of follow-up: 90 days (both arms)
Primary outcome measure(s) Proportion of eligible patients enrolled in the CHAT Pilot Trial. Feasibility for the pilot study will be assessed by metrics that reflect our capacity to ultimately recruit a representative sample of 1050 patients in the planned full CHAT trial. We will consider the study to be feasible if we recruit at least 30% (commonly used threshold in ICU studies) of all eligible patients in participating ICUs through careful review of site screening logs.
Secondary outcome measure(s) 1. Adherence to the medication administration regimen as outlined in the study protocol
2. Proportion of completed primary and secondary endpoints for the planned full CHAT trial that are collected
3. The number of patients who receive open-label statins
4. The number of consent withdrawals
5. Recruitment rates by approved consent model

All outcomes will be measured upon termination of this pilot study. However, adherence to medication administration will be recorded daily on study days 1 through 14 for each study subject.
Sources of funding 1. Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: 102785)
2. Public Health Agency of Canada (PHAC) (Canada) (ref: 09-137443-391)
3. Physician's Services Incorporated (PSI) Foundation (Canada)
Trial website
Publications
Contact name Dr  John  Marshall
  Address St. Michael's Hospital
30 Bond Street
  City/town Toronto
  Zip/Postcode M5B 1W8
  Country Canada
  Tel +1 416 864 6060 ext. 5225
  Fax +1 416 864 5349
  Email MarshallJ@smh.toronto.on.ca
Sponsor St Michael's Hospital (UK)
  Address 30 Bond Street
  City/town Toronto
  Zip/Postcode M5B 1W8
  Country Canada
  Sponsor website: http://www.stmichaelshospital.com/
Date applied 23/02/2010
Last edited 29/11/2010
Date ISRCTN assigned 08/03/2010
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