Collaborative H1N1 Adjuvant Treatment Pilot Trial

NCT ID: NCT01033955

Last Updated: 2013-02-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2010-07-31

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.

Conditions

Critically Ill; H1N1/Influenza Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Rosuvastatin

Intervention Type: DRUG

Loading dose: 40 mg (day 1) Maintenance dose: 20 mg (days 2-14)

Placebo

An identical appearing placebo will be administered to patients in the second study arm.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

identical appearing encapsulated placebo.

Interventions

Rosuvastatin

Loading dose: 40 mg (day 1) Maintenance dose: 20 mg (days 2-14)

Intervention Type: DRUG

Placebo

identical appearing encapsulated placebo.

Intervention Type: DRUG

Other Intervention Names

Crestor

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role: collaborator

Public Health Agency of Canada (PHAC)

OTHER_GOV

Sponsor Role: collaborator

Canadian Critical Care Trials Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John C Marshall, MD, FRCPS

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Karen EA Burns, MD,FRCPC,MSc

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Locations

Vancouver General Hospital

Vancouver, British Columbia, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

Health Sciences Centre

Winnipeg, Manitoba, Canada

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Hopital Laval

Québec, Quebec, Canada

Centre hospitalier universitaire de Sherbrooke (CHUS)

Sherbrooke, Quebec, Canada

Countries

Canada

Other Identifiers

001 CHAT 2009

Identifier Type: -

Identifier Source: org_study_id