Fluid Resuscitation in Early Septic Shock

NCT00819416 | Completed Phase 2 DMC

• 1 other identifier: 2008640
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 6

Brief Summary

Severe infection in the intensive care unit is common accounting for about 10% of admissions and has a death rate of approximately 40-50%. It is almost always associated with significant reductions in blood pressure. Administration of fluid often in large volumes is essential to normalize blood pressure and prevent failure of organs and death. Two common classes of fluid solutions are crystalloid fluids (salt based, normal saline) and colloid fluids (protein based, albumin). Due to its properties, the albumin fluid may remain in the vascular space better than the normal saline solution. Hence, there may be faster attainment of normal blood pressure as well as a reduction in failed organs and death. Preliminary clinical trial data suggests a potential for benefit with albumin in this setting but these findings require confirmation in a large clinical trial. There are few data to explain how albumin may exert its protective effects and lead to better outcomes for patients with severe infections. We will conduct a clinical study that will examine potential biological mechanisms for albumin's protective effects in 50 patients across 6 Canadian academic hospitals. We will also examine our ability to successfully recruit patients into this trial. This study will provide information that will help to understand the biological mechanisms of albumin in severe infection. The information gained will guide the investigative team for future fluid related mechanistic questions. The study will also provide essential information that will aid in the design and conduct of the future large clinical trial that will examine death as its primary outcome.

Conditions

Septic Shock; Sepsis; Severe Sepsis

Keywords

randomized controlled trial; clinical trial

Outcome Measures

Primary Outcomes (1)

• Comparison of thrombin generation and protein C and APC levels

  Thrombin generation at 72 hours and protein C and APC levels at 7 days after randomization

Secondary Outcomes (1)

• Comparison of blood and urine pro and anti-inflammatory cytokine and chemokine levels.Clinical outcomes include mortality, length of stay,organ failure, and organ support measures.

  Inflammatory markers measured first 7 days of care. Mortality in ICU/hospital/30 days. Length of stay ICU/hospital. Organ failure first 7 days of care.

Study Arms (2)

1

EXPERIMENTAL

5% albumin

Drug: 5% albumin

2

OTHER

Normal saline

Drug: Normal Saline

Interventions

5% albumin DRUG

5% albumin for the first 7 days of care in the ICU

Also known as: colloid fluid

1

Normal Saline DRUG

Normal Saline for the first 7 days of care in the ICU

Also known as: crystalloid fluid

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Refractory Hypotension: The patient has received at least 1 litre of normal saline or ringers lactate crystalloid fluid for hypotension (defined as a systolic blood pressure less than 90 mm Hg, or a systolic blood pressure more than 40 mm Hg below baseline, or a mean arterial blood pressure less than 65 mm Hg) within 8 hours of the first hypotensive event and has refractory hypotension defined by: a) Presence of hypotension OR b) Initiation of a vasopressor agent(s).
• Two or more criteria for the systemic inflammatory response syndrome (SIRS): i) heart rate greater than 90 beats per minute; ii) respiratory rate greater than 20 breathes per minute, or a PaC02 less than 32 mm Hg, or mechanically ventilated; iii) temperature greater than 38 or less than 36 degrees Celsius; iv) or a white blood cell count greater than 12,000 x 109/L or less than 4,000 x 109/L, or more than 10% bands on the differential.

You may not qualify if:

• Clinically apparent other forms of shock including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax) or hemorrhagic shock
• Previous admission to ICU with severe sepsis or septic shock during the index hospitalization
• More than 250 mls of colloid fluid (Pentaspan, Voluven, Hextend, or albumin) from the first episode of hypotension
• A known previous severe reaction to albumin
• Burns
• Known cirrhosis
• Traumatic brain injury
• Religious objection to albumin use
• Less than 18 years of age
• Pregnant
• Family or patient not committed to aggressive care
• Currently enrolled in another related interventional study.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Blood Services: collaborator
• Baxter Healthcare Corporation: collaborator

Study Sites (6)

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Winnipeg Health Sciences Center

Winnipeg, Manitoba, R3P 0X1, Canada

Location

Halifax Capital Health Center

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Hôpital de l'Enfant-Jésus

Québec, Quebec, G1J 1Z4, Canada

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Albumins; Saline Solution

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Lauralyn A McIntyre, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Alan Tinmouth, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Alison Fox Robichaud, MD

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 8, 2009
• First Posted: January 9, 2009
• Study Start: February 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: February 1, 2010
• Last Updated: April 14, 2010

Record last verified: 2010-04

Locations

CA (6)