Collaborative H1N1 Adjuvant Treatment pilot trial

ISRCTN	ISRCTN45190901
DOI	https://doi.org/10.1186/ISRCTN45190901
ClinicalTrials.gov number	NCT01033955
Secondary identifying numbers	102785

Submission date: 23/02/2010
Registration date: 08/03/2010
Last edited: 08/03/2019

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr John Marshall
Scientific

St. Michael's Hospital
30 Bond Street
Toronto
M5B 1W8
Canada

Phone	+1 416 864 6060 ext. 5225
Email	MarshallJ@smh.toronto.on.ca

Study information

Study design	Double blind placebo controlled pilot randomised trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study acronym	CHAT
Study objectives	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.
Ethics approval(s)	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.
Health condition(s) or problem(s) studied	Critically ill influenza A/H1N1 infection
Intervention	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)
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Rosuvastatin (Crestor®)
Primary outcome measure	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 measures	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.
Overall study start date	01/01/2010
Completion date	30/08/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	80
Key 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
Key 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
Date of first enrolment	01/01/2010
Date of final enrolment	30/08/2011

Locations

Countries of recruitment

Argentina
Australia
Canada
Mexico
New Zealand
Saudi Arabia

Study participating centre

St. Michael's Hospital

Toronto
M5B 1W8
Canada

Sponsor information

St Michael's Hospital (UK)
Hospital/treatment centre

30 Bond Street
Toronto
M5B 1W8
Canada

Website	http://www.stmichaelshospital.com/
"ROR"	https://ror.org/04skqfp25

Funders

Funder type

Research organisation

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: 102785)

No information available

Public Health Agency of Canada (PHAC) (Canada) (ref: 09-137443-391)

No information available

Physician's Services Incorporated (PSI) Foundation (Canada)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	01/12/2011		Yes	No

Editorial Notes

08/03/2019: Publication reference added.