Collaborative H1N1 Adjuvant Treatment Pilot Trial (CHAT)

Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial

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).

Study Overview

• Status: Terminated
• Conditions: Critically Ill; H1N1/Influenza Infection
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3B 0Z3
      • Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Quebec City, Quebec, Canada, G1V 4G5
      • Hôpital Laval
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre hospitalier universitaire de Sherbrooke (CHUS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug (Rosuvastatin) Crestor; The first dose of encapsulated study drug or placebo (day 1) will be administered within 4 hours of randomization as a loading dose of 40 mg. The placebo will be identical in appearance to Rosuvastatin. Thereafter, doses of 20 mg will be administered daily starting on the next calendar day at 10 pm daily (+/- 4 hours) as a maintenance dose from days 2 to 14. If the patient is of Asian descent, is <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.	Drug: Rosuvastatin; Loading dose: 40 mg (day 1) Maintenance dose: 20 mg (days 2-14); Other Names: Crestor
Placebo Comparator: Placebo; An identical appearing placebo will be administered to patients in the second study arm.	Drug: Placebo; identical appearing encapsulated placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of eligible patients enrolled in the CHAT Pilot Trial.	anticipated 6 months (duration of pandemic)

Secondary Outcome Measures

Outcome Measure	Time Frame
Adherence to the medication regimen as outlined in the study protocol.	14 day treatment course
Proportion of completed primary and secondary endpoints collected for the planned full CHAT trial	90 days
The number of study withdrawals due to administration of open label statins and consent withdrawals	anticipated 6 month study period

Collaborators and Investigators

• Sponsor: Canadian Critical Care Trials Group
• Collaborators: Canadian Institutes of Health Research (CIHR); The Physicians' Services Incorporated Foundation; Public Health Agency of Canada (PHAC)
• Investigators: Principal Investigator: John C Marshall, MD, FRCPS, Unity Health Toronto; Principal Investigator: Karen EA Burns, MD,FRCPC,MSc, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: December 16, 2009
• First Submitted That Met QC Criteria: December 16, 2009
• First Posted (Estimate): December 17, 2009

Study Record Updates

• Last Update Posted (Estimate): February 21, 2013
• Last Update Submitted That Met QC Criteria: February 20, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: critical care; critically ill patients; invasive mechanical ventilation; respiration; ventilation, artificial; H1N1/influenza infection; H1N1/influenza infection (suspected, probable or confirmed)
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Disease Attributes; Orthomyxoviridae Infections; Infections; Influenza, Human; Critical Illness; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: 001 CHAT 2009