A Randomized Trial of GM-CSF in Patients With ALI/ARDS

NCT00201409 | Completed Phase 2 Results DMC

• 2 other identifiers: 258P50HL074024
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 3

Brief Summary

This study will test the hypothesis that administration of granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) will improve the clinical course and outcome by shortening the duration of mechanical ventilation for these patients.

Conditions

Respiratory Distress Syndrome, Adult

Outcome Measures

Primary Outcomes (1)

• Ventilator-free Days During Days 1-28

  Measured at Day 28

Secondary Outcomes (2)

• Oxygenation Index Change at Day 15 From Day 1

  Day 1, Day 15

• Days Without Organ Failure

  Measured at Day 28

Study Arms (2)

1

EXPERIMENTAL

Participants will be randomized to receive recombinant human GM-CSF (250 mcg/M2).

Drug: GM-CSF

2

PLACEBO COMPARATOR

Participants will be randomized to receive placebo.

Drug: Placebo

Interventions

Placebo DRUG

Placebo will be administered by slow intravenous infusion once daily for 14 days.

2

GM-CSF DRUG

Recombinant human GM-CSF (250 mcg/M2) will be administered by slow intravenous infusion once daily for 14 days.

1

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute onset of illness with:
• PaO2/FiO2 ratio of less than 300 (ALI) or PaO2/FiO2 ratio of less than 200 (ARDS)
• Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph (infiltrates may be patchy, diffuse, homogeneous, or asymmetric)
• Requirement for positive pressure ventilation via an endotracheal tube
• No clinical evidence of left atrial hypertension (pulmonary arterial wedge pressure measure up to 18 mm Hg)
• First three criteria must occur together within a 24-hour interval

You may not qualify if:

• Greater than 7 days elapsed following institution of mechanical ventilation
• Pregnancy
• Chronic respiratory failure as defined by any of the following: 1) FEV1 less than 20 ml/kg of PBW; or 2) FEV1/FVC less than 50%
• Chronic hypercapnia or hypoxemia
• Hospitalization within the past 6 months for acute respiratory failure
• Chronic home use of oxygen or mechanical ventilation
• Left ventricular failure as defined by New York Heart Association (NYHA) class IV status
• Neutropenia (absolute neutrophil count less than 1000 cells/mm3)
• History of hematological malignancy or bone marrow transplant
• Entry into other intervention clinical trials
• Decision of the patient or attending physician to forego aggressive care
• Expected survival rate of less than 6 months (based solely on pre-existing medical problems \[i.e., poorly controlled neoplasm or other end-stage disease\])
• AIDS or known history of HIV infection
• Prednisone (or equivalent) therapy greater than or equal to 20 mg/day for a period of not less than 2 months with treatment continuing within 3 weeks prior to screening
• Cytotoxic therapy within 3 weeks of screening

Sponsors & Collaborators

• University of Michigan: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Emory University: collaborator
• University of Colorado, Denver: collaborator

Study Sites (3)

University of Colorado Health Sciences Center

Denver, Colorado, 80045, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (7)

• Paine R 3rd, Wilcoxen SE, Morris SB, Sartori C, Baleeiro CE, Matthay MA, Christensen PJ. Transgenic overexpression of granulocyte macrophage-colony stimulating factor in the lung prevents hyperoxic lung injury. Am J Pathol. 2003 Dec;163(6):2397-406. doi: 10.1016/S0002-9440(10)63594-8.

  PMID: 14633611 BACKGROUND

• Paine R 3rd, Morris SB, Jin H, Wilcoxen SE, Phare SM, Moore BB, Coffey MJ, Toews GB. Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice. Am J Physiol Lung Cell Mol Physiol. 2001 Nov;281(5):L1210-8. doi: 10.1152/ajplung.2001.281.5.L1210.

  PMID: 11597913 BACKGROUND

• Baleeiro CE, Wilcoxen SE, Morris SB, Standiford TJ, Paine R 3rd. Sublethal hyperoxia impairs pulmonary innate immunity. J Immunol. 2003 Jul 15;171(2):955-63. doi: 10.4049/jimmunol.171.2.955.

  PMID: 12847267 BACKGROUND

• Presneill JJ, Harris T, Stewart AG, Cade JF, Wilson JW. A randomized phase II trial of granulocyte-macrophage colony-stimulating factor therapy in severe sepsis with respiratory dysfunction. Am J Respir Crit Care Med. 2002 Jul 15;166(2):138-43. doi: 10.1164/rccm.2009005.

  PMID: 12119223 BACKGROUND

• Matute-Bello G, Liles WC, Radella F 2nd, Steinberg KP, Ruzinski JT, Hudson LD, Martin TR. Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome. Crit Care Med. 2000 Jan;28(1):1-7. doi: 10.1097/00003246-200001000-00001.

  PMID: 10667491 BACKGROUND

• Spencer-Segal JL, Hyzy RC, Iwashyna TJ, Standiford TJ. Psychiatric Symptoms in Survivors of Acute Respiratory Distress Syndrome. Effects of Age, Sex, and Immune Modulation. Ann Am Thorac Soc. 2017 Jun;14(6):960-967. doi: 10.1513/AnnalsATS.201606-468OC.

  PMID: 28358594 DERIVED

• Paine R 3rd, Standiford TJ, Dechert RE, Moss M, Martin GS, Rosenberg AL, Thannickal VJ, Burnham EL, Brown MB, Hyzy RC. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med. 2012 Jan;40(1):90-7. doi: 10.1097/CCM.0b013e31822d7bf0.

  PMID: 21926600 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Robert Hyzy
• Organization: University of Michigan

rhyzy@umich.edu

7349365201

Study Officials

• Robert Paine, MD

  University of Utah and University of Michigan

  STUDY DIRECTOR

• Robert C. Hyzy, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: July 1, 2004
• Primary Completion: May 1, 2009
• Study Completion: June 1, 2009
• Last Updated: December 29, 2015
• Results First Posted: April 27, 2015

Record last verified: 2015-11

Locations

US (3)