Clinical trial NCT01033955: Collaborative H1N1 Adjuvant Treatment Pilot Trial
Official title: Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Critically Ill
H1N1/Influenza Infection
Keywords: critical care
H1N1/influenza infection
respiration
ventilation, artificial
critically ill patients
invasive mechanical ventilation
H1N1/influenza infection (suspected, probable or confirmed)
Lead sponsor: Canadian Critical Care Trials Group
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: The Physicians' Services Incorporated Foundation
name: Public Health Agency of Canada (PHAC)
First posted: 2009-12-17
Enrollment: 8
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study Design: A, multinational, double blind, placebo-controlled pilot RCT involving 80 patients in the general ICUs of 30 centres. Most patients will be recruited from within Canada; however cases will be recruited from international sites. This study will be conducted under the auspices of the Canadian Critical Care Trials Group (CCCTG) and the International Forum for Acute Care Trialists (InFACT).

Detailed description: Primary Objective: The primary objective of the CHAT Pilot Trial is to assess our ability to recruit the desired patient population (i.e., the proportion of eligible patients enrolled in the trial), and to conduct a scientifically rigorous international RCT under pandemic circumstances.

Secondary Objectives: To evaluate (i) adherence to the medication administration regimen. (ii) the ability for research staff to collect the required primary and secondary endpoints for the planned full CHAT trial, (iii) the number of study withdrawals due to administration of open-label statins and withdrawals of consent and (iv) the impact of the approved consent model on recruitment rates.

Study Methods (Overview): Using a web-based randomization system patients, research coordinators will assign critically ill adults treated with antiviral medication for \< or equal to 72 hours and requiring mechanical ventilation to one of two treatment strategies (rosuvastatin or placebo) for 14 days. Given the need to recruit patients into the CHAT Trial under pandemic conditions, when family members may not be present to provide written informed consent, we will request either a waiver of consent or deferred consent from Research Ethics Boards (REBs) at participating centres. The Keenan Research Centre/Li Ka Shing Knowledge Institute (St Michael's Hospital, Toronto, Ontario) will be the study Methods Centre.

Eligibility criteria: Inclusion Criteria:

1. Critically ill adult patients \> or equal to 16 years of age admitted to an adult ICU for any reason with suspected, probable or confirmed influenza infection
2. Requiring mechanical ventilation (invasive or non-invasive)
3. Receiving antiviral therapy (any medication at any dose and for any intended duration) for \< or equal to 72 hours
4. Attending physician or intensivist must have a 'moderate' to 'high' index of suspicion for influenza

Exclusion Criteria:

1. Age \< 16 years
2. Do not resuscitate or re-intubate order documented on chart or anticipated withdrawal of life support
3. Weight \< 40 kg
4. Unable to receive or unlikely to absorb enteral study drug (e.g. incomplete or complete bowel obstruction, intestinal ischemia, infarction, short bowel syndrome)
5. Rosuvastatin specific exclusions:

   * Already receiving a statin (Atorvastatin, Lovastatin, Simvastatin, Pravastatin, Rosuvastatin)
   * Allergy or intolerance to statins
   * Receiving niacin, fenofibrate, cyclosporine, gemfibrozil, lopinavir, ritonavir or planned use of oral contraceptives or estrogen therapy during the ICU stay
   * CK exceeds 10 times ULN or ALT exceeds 8 times the ULN
6. Severe chronic liver disease (Child-Pugh Score 11-15)
7. Previous enrollment in this trial
8. Pregnancy or breast feeding
9. At the time of enrollment, patients must not have received \>72 hours of antiviral therapy

Primary outcomes:
measure: Proportion of eligible patients enrolled in the CHAT Pilot Trial.
timeFrame: anticipated 6 months (duration of pandemic)
Secondary outcomes:
measure: Adherence to the medication regimen as outlined in the study protocol.
timeFrame: 14 day treatment course
measure: Proportion of completed primary and secondary endpoints collected for the planned full CHAT trial
timeFrame: 90 days
measure: The number of study withdrawals due to administration of open label statins and consent withdrawals
timeFrame: anticipated 6 month study period
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Quebec City
country: Canada
facility: Hopital Laval
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke (CHUS)
state: Quebec
Study officials:
affiliation: Unity Health Toronto
name: John C Marshall, MD, FRCPS
role: PRINCIPAL_INVESTIGATOR
affiliation: Unity Health Toronto
name: Karen EA Burns, MD,FRCPC,MSc
role: PRINCIPAL_INVESTIGATOR
References: