Acute Respiratory Distress Network (ARDSNet) Studies 01 and 03 Lower versus higher tidal volume, ketoconazole treatment and lisofylline treatment (ARMA/KARMA/LARMA) - Catalog

  • Name

    Acute Respiratory Distress Network (ARDSNet) Studies 01 and 03 Lower versus higher tidal volume, ketoconazole treatment and lisofylline treatment (ARMA/KARMA/LARMA)

  • Accession Number

    HLB00240315a

  • Acronym

    ARDSNet-ARMA/KARMA/LARMA

  • Related studies
  • BSI Study IDs

    AR1

    AR3

  • Is public use dataset

    False

  • Keywords
  • Ingestion Status
    Released
  • Has Study Datasets

    True

  • Has Specimens

    True

  • Specimen ID Type
    Coded
  • Study Website

    http://www.ardsnet.org/

  • The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.

    False

  • Clinical Trial URLs
  • Study type
    Clinical Trial
  • Collection Type
    Open BioLINCC Study
  • Cohort type
    Adult
  • Interventions

    Procedure: Low Tidal Volume VentilationProcedure: Positive End-Expiratory PressureDrug: LysofyllineDrug: MethylprednisoloneDrug: KetoconazoleProcedure: Fluid ManagementProcedure: Pulmonary Artery Catheter

  • Study Open Date (Data)

    2009-10-01

  • Study Open Date (Specimens)

    2010-04-09

  • Date materials available

    2008-10-13

  • Last updated

    2006-08-24

  • Study period

    1996-1999

  • Study Contacts
  • NHLBI Division

    DLD

  • Classification
    Lung
  • HIV study classification
    non-HIV
  • COVID study classification
    non-COVID
  • Pre-Website # of Specimens Shipped

    10604

  • # of Returned Specimens

    0

  • Primary Publication URLs
  • Conditions
    ALI
    ARDS
    Acute Lung Injury
    Lung Diseases
    Respiratory Distress Syndrome, Adult
  • Objectives

    The ARDS Network is a consortium of clinical centers and a coordinating center to design and test novel therapies for the treatment of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). The primary objective of the KARMA trial was to investigate the efficacy and safety of Ketoconazole and Respiratory Management in the treatment of ALI and ARDS. The Ketoconazole arm of the study was later stopped due to an inability to show efficacy. Patients continued to be randomized to the respiratory management arms of the study (ARMA), which compared two ventilator strategies: a tidal volume of 6 mL/kg versus 12 mL/kg. The LARMA phase of the study investigated the efficacy of Lisofylline and Respiratory Management.

  • Background

    Patients suffering from ARDS are extremely ill, require mechanical ventilation and, despite improvements in medical care and technology, had a mortality rate as high as 50 percent. An excessive inflammatory response is characteristic of ALI of which ARDS represents the most severe end of the pathophysiologic spectrum. The inflammatory response includes increased numbers of neutrophils activated to produce cytokines, proteases, and reactive oxygen intermediates. Pulmonary injury may also be enhanced by alveolar and tissue macrophages as a producer of vasoactive substances, neutrophil chemoattractants, and procoagulant substances. Ketoconazole, a synthetic antifungal imidazole, also has anti-inflammatory activities and may inhibit neutrophil recruitment via several different pathways known to be involved in the development of ALI and ARDS. Lisofylline causes a marked decrease in the circulating levels of the major oxidizable species of free fatty acids and also inhibits proinflammatory intracellular signaling. Mechanical ventilation in patients with ALI and ARDS have traditionally used tidal volumes of 10 to 15 ml per kilogram of body weight. These large tidal volumes are often necessary to achieve normal partial pressure of arterial carbon dioxide and pH, but may induce inflammatory responses through disruption of pulmonary epithelium and endothelium. Mechanical ventilation at lower tidal volumes may reduce injurious lung stretch and decrease the inflammatory response.

  • Participants

    Patients were recruited from hospitals at the 10 University centers of the ARDS Network and were eligible if: they were in an ICU and required positive pressure ventilation, had acute onset of significantly impaired oxygenation (PaO2 to FIO2 300), bilateral infiltrates consistent with pulmonary edema, no clinical evidence of left atrial hypertension, and were enrolled within 36 hours of developing these criteria. Exclusion criteria included age less than 18, participation in other clinical trials within the previous 30 days, pregnancy, increased intracranial pressure, neurologic conditions that could impair weaning from ventilator support, chronic respiratory disease, sickle cell disease, burns covering more than 30% of body surface area, bone or marrow transplant history, or comorbid irreversible conditions with a six month mortality rate of at least 50 percent. The Ketoconazole and Lisofylline trials were designed as 2 x 2 factorials and included 220 patients in each trial. A total of 860 patients were randomized into the ventilator management trial. Patients enrolled in the Lisofylline or Ketoconozole studies had to be concurrently enrolled in the ventilator management study and were first randomized into a ventilator strategy and then to drug or placebo.

  • Design
  • Conclusions

    Ketoconazole was found to be safe but did not reduce mortality, duration of mechanical ventilation, or improve lung function. Lisofylline was also found to be safe and to have no beneficial effect for patients with ALI or ARDS. Ventilation at lower tidal volumes resulted in reduced mortality and an increase in the number of days without ventilator support. (JAMA, 2000; 283:1995-2002; Crit Care Med, 2002; 30: 1-6; N Engl J Med, 2000; 342: 1301-1308).

  • Disease classification
  • Publications
  • Mat types
    Plasma
    Serum
    Urine
  • Network
    Acute Respiratory Distress Network (ARDSNet)

The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.

  • Subjects

    ARDSNet01: 667

    ARDSNet01 and ARDSNet03: 194

    ARDSNet03: 41


    Last Modified: June 22, 2022, 10:25 a.m.
  • Age

     

    ARDSNet01

    ARDSNet01 and ARDSNet03

    ARDSNet03

    All

    N

    %

    N

    %

    N

    %

    N

    %

    16-20

    14

    2.10

    4

    2.06

    1

    2.44

    19

    2.11

    21-25

    25

    3.75

    6

    3.09

    2

    4.88

    33

    3.66

    26-30

    43

    6.45

    14

    7.22

    2

    4.88

    59

    6.54

    31-35

    54

    8.10

    16

    8.25

    2

    4.88

    72

    7.98

    36-40

    61

    9.15

    23

    11.86

    3

    7.32

    87

    9.65

    41-45

    61

    9.15

    20

    10.31

    7

    17.07

    88

    9.76

    46-50

    75

    11.24

    25

    12.89

    4

    9.76

    104

    11.53

    51-55

    54

    8.10

    14

    7.22

    2

    4.88

    70

    7.76

    56-60

    58

    8.70

    11

    5.67

    1

    2.44

    70

    7.76

    61-65

    51

    7.65

    13

    6.70

    1

    2.44

    65

    7.21

    66-70

    52

    7.80

    18

    9.28

    6

    14.63

    76

    8.43

    71-75

    54

    8.10

    16

    8.25

    6

    14.63

    76

    8.43

    76-80

    32

    4.80

    10

    5.15

    2

    4.88

    44

    4.88

    81-85

    26

    3.90

    3

    1.55

    2

    4.88

    31

    3.44

    86-90

    7

    1.05

    1

    0.52

    .

    .

    8

    0.89

     

    Last Modified: June 22, 2022, 10:25 a.m.
  • Sex

     

    ARDSNet01

    ARDSNet01 and ARDSNet03

    ARDSNet03

    All

    N

    %

    N

    %

    N

    %

    N

    %

    Unknown

    .

    .

    .

    .

    1

    2.44

    1

    0.11

    Female

    392

    58.77

    121

    62.37

    23

    56.10

    536

    59.42

    Male

    275

    41.23

    73

    37.63

    17

    41.46

    365

    40.47

     

    Last Modified: June 22, 2022, 10:25 a.m.
  • Race

     

    ARDSNet01

    ARDSNet01 and ARDSNet03

    ARDSNet03

    All

    N

    %

    N

    %

    N

    %

    N

    %

    White non-Hispanic

    482

    72.26

    147

    75.77

    32

    78.05

    661

    73.28

    Black non-Hispanic

    118

    17.69

    31

    15.98

    6

    14.63

    155

    17.18

    Other

    67

    10.04

    16

    8.25

    3

    7.32

    86

    9.53

     

    Last Modified: June 22, 2022, 10:25 a.m.

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. PDF Section 3.0 of the BioLINCC Handbook describes the components of the review process.

  • Material Types

    Last Modified: Nov. 30, 2015, 10:17 a.m.
  • General Freeze/Thaw Status
  • Visits (Vials)

    06/22/2022

      Serum Plasma Urine Total
    Day 0 834 1,532 1,153 3,519
    Day 1 0 3,501 1,144 4,645
    Day 3 771 3,292 1,030 5,093
    Day 21 0 1 0 1
    Unknown 0 78 2 80

    Last Modified: June 22, 2022, 10:25 a.m.
  • Visits (Subjects)

    06/22/2022

      Serum
    Total number of subjects Average volume (ml) per subject
    Day 0 223 2.30
    Day 3 207 5.55
     
      Plasma
    Total number of subjects Average volume (ml) per subject
    Day 0 653 2.86
    Day 1 832 3.24
    Day 3 765 3.57
    Day 21 1 4.50
    Unknown 61 3.20
     
      Urine
    Total number of subjects Average volume (ml) per subject
    Day 0 559 3.02
    Day 1 581 2.88
    Day 3 506 2.99
    Unknown 2 1.80

     

    Last Modified: June 22, 2022, 10:25 a.m.