Intrapleural Methylprednisolone Injection for Multiple Organ Failure With Acute Respiratory Distress Syndrome

NCT01423864 | Completed Phase 2

• 1 other identifier: 200906014R
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Acute respiratory distress syndrome (ARDS) in combination with multi-organ dysfunction syndrome (MODS) is a life-threatening condition, particularly when treatment modalities such as extracorporeal membrane oxygenation (ECMO) and catecholamine administration have failed to treat the severe condition. In this study, the investigators report patients who responded to intrapleural steroid instillation (IPSI) while being unresponsive to conventional treatment (use of intravenous steroids, nitric oxide inhalation, high-frequency oscillatory ventilation, or ECMO) for treatment of critical illnesses such as ARDS in combination with MODS.

Conditions

Acute Respiratory Distress Syndrome (ARDS); Multiple Organ Failure

Keywords

Acute Respiratory Distress Syndrome; Multi-organ Dysfunction Syndrome; Extracorporeal Membrane Oxygenation

Outcome Measures

Primary Outcomes (1)

• survival until discharge from the hospital

  Comparing the difference between two groups about the survival ratio of discharge from the hospital

  2005~2009 (up to 4 years)

Secondary Outcomes (3)

• Incidence of complications

  12 weeks

• the effects on tidal volumes

  up to 12 weeks

• the therapeutic effects on oxygenation

  up to 12 weeks

Study Arms (2)

conventional ECMO with intravenous steroid

SHAM COMPARATOR

refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome unresponsive to conventional extracorporeal membrane oxygenation

Drug: conventional ECMO with intravenous steroid

Drug: intrapleural steroid instillation

EXPERIMENTAL

refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome unresponsive to conventional extracorporeal membrane oxygenation

Drug: solumedrol

Interventions

conventional ECMO with intravenous steroid DRUG

refractory acute respiratory distress syndrome and multi-organ dysfunction syndrome treated with intravenous steroid, Solu-Cortef 50mg q6h taper down when hemodynamic stable

Also known as: Solu-Cortef

conventional ECMO with intravenous steroid

solumedrol DRUG

Initially, intrapleural steroid administration was performed using 40 mg solumedrol q6h (for both the pleural cavities). If chest radiography showed an improvement in consolidation, i.e., 0.8 \> FiO2 ≥ 0.5 and 5 ≤ PEEP ≤ 10, the dosage of solumedrol was reduced to 40 mg q12h. When FiO2 was below 0.5 and the PEEP was below 10, the dosage of solumedrol was lowered to 40 mg qd for 3 days and then its administration was discontinued.

Drug: intrapleural steroid instillation

Eligibility Criteria

• Age: 16 Years - 87 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All of the patients had failure of at least 2 organs acquiring arteriovenous or venovenous ECMO support
• All of the patients met the criteria as below:
• blood gas parameters of PaO2/FiO2 \< 100
• bilateral pulmonary infiltration on chest radiographic images
• % oxygen demand in case of ventilation and ECMO flow
• hemodynamic instability requiring high catecholamine infusion
• All the patients had scoring system, which were calculated by the physician within 24 h of admission of the patients into the hospital.
• sequential organ failure assessment score (SOFA) ≥ 10
• Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 20
• inotropic score ≥ 10
• multiple organ dysfunction (MOD) score ≥ 10

You may not qualify if:

• uncontrollable underlying disease
• life expectancy of less than 24 h
• immunosuppression
• neutrophil count of less than 0.3 × 109/L
• brainstem death
• history of long-term corticosteroid use during the past 6 months.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Department of Surgery, National Taiwan University Hospital

7, Chung-Shan S. Rd, Taipei 10002, Taiwan., Taiwan, 10002, Taiwan

Location

Related Publications (19)

• Zhang J, Wang W, Sun J, Li Q, Liu J, Zhu H, Chen T, Wang H, Yu S, Sun G, Chen W, Yi D. Gap junction channel modulates pulmonary vascular permeability through calcium in acute lung injury: an experimental study. Respiration. 2010;80(3):236-45. doi: 10.1159/000274384. Epub 2010 Jan 7.

  PMID: 20090287 BACKGROUND

• Suchyta MR, Clemmer TP, Orme JF Jr, Morris AH, Elliott CG. Increased survival of ARDS patients with severe hypoxemia (ECMO criteria). Chest. 1991 Apr;99(4):951-5. doi: 10.1378/chest.99.4.951.

  PMID: 2009801 BACKGROUND

• Biffl WL, Moore FA, Moore EE, Haenel JB, McIntyre RC Jr, Burch JM. Are corticosteroids salvage therapy for refractory acute respiratory distress syndrome? Am J Surg. 1995 Dec;170(6):591-5; discussion 595-6. doi: 10.1016/s0002-9610(99)80022-1.

  PMID: 7492007 BACKGROUND

• Brunet F, Mira JP, Belghith M, Monchi M, Renaud B, Fierobe L, Hamy I, Dhainaut JF, Dall'ava-Santucci J. Extracorporeal carbon dioxide removal technique improves oxygenation without causing overinflation. Am J Respir Crit Care Med. 1994 Jun;149(6):1557-62. doi: 10.1164/ajrccm.149.6.8004313.

  PMID: 8004313 BACKGROUND

• Wiener-Kronish JP, Broaddus VC. Interrelationship of pleural and pulmonary interstitial liquid. Annu Rev Physiol. 1993;55:209-26. doi: 10.1146/annurev.ph.55.030193.001233.

  PMID: 8466174 BACKGROUND

• Lewandowski K, Rossaint R, Pappert D, Gerlach H, Slama KJ, Weidemann H, Frey DJ, Hoffmann O, Keske U, Falke KJ. High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation. Intensive Care Med. 1997 Aug;23(8):819-35. doi: 10.1007/s001340050418.

  PMID: 9310799 BACKGROUND

• Dagenais A, Denis C, Vives MF, Girouard S, Masse C, Nguyen T, Yamagata T, Grygorczyk C, Kothary R, Berthiaume Y. Modulation of alpha-ENaC and alpha1-Na+-K+-ATPase by cAMP and dexamethasone in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2001 Jul;281(1):L217-30. doi: 10.1152/ajplung.2001.281.1.L217.

  PMID: 11404265 BACKGROUND

• Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. doi: 10.1001/jama.288.7.862.

  PMID: 12186604 BACKGROUND

• North SA, Au HJ, Halls SB, Tkachuk L, Mackey JR. A randomized, phase III, double-blind, placebo-controlled trial of intrapleural instillation of methylprednisolone acetate in the management of malignant pleural effusion. Chest. 2003 Mar;123(3):822-7. doi: 10.1378/chest.123.3.822.

  PMID: 12628884 BACKGROUND

• Gerlach H, Keh D, Semmerow A, Busch T, Lewandowski K, Pappert DM, Rossaint R, Falke KJ. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study. Am J Respir Crit Care Med. 2003 Apr 1;167(7):1008-15. doi: 10.1164/rccm.2108121.

  PMID: 12663340 BACKGROUND

• Broccard AF. Prone position in ARDS: are we looking at a half-empty or half-full glass? Chest. 2003 May;123(5):1334-6. doi: 10.1378/chest.123.5.1334. No abstract available.

  PMID: 12740242 BACKGROUND

• Dunser M, Hasibeder W, Rieger M, Mayr AJ. Successful therapy of severe pneumonia-associated ARDS after pneumonectomy with ECMO and steroids. Ann Thorac Surg. 2004 Jul;78(1):335-7. doi: 10.1016/S0003-4975(03)01264-5.

  PMID: 15223462 BACKGROUND

• Tomiyama H, Takara I, Tokumine J, Sugahara K. [Sivelestat sodium hydrate was effective for ARDS in a patient suffering from chronic rheumatoid arthritis with acute exacerbation after failing to respond to high dose steroid pulse therapy]. Masui. 2004 Sep;53(9):1042-6. Japanese.

  PMID: 15500109 BACKGROUND

• Zemans RL, Matthay MA. Bench-to-bedside review: the role of the alveolar epithelium in the resolution of pulmonary edema in acute lung injury. Crit Care. 2004 Dec;8(6):469-77. doi: 10.1186/cc2906. Epub 2004 Jun 30.

  PMID: 15566618 BACKGROUND

• Shinozaki M. [Respiratory and cadiovascular management of septic ALI-ARDS and shock]. Nihon Rinsho. 2004 Dec;62(12):2301-7. Japanese.

  PMID: 15597800 BACKGROUND

• Lee HS, Lee JM, Kim MS, Kim HY, Hwangbo B, Zo JI. Low-dose steroid therapy at an early phase of postoperative acute respiratory distress syndrome. Ann Thorac Surg. 2005 Feb;79(2):405-10. doi: 10.1016/j.athoracsur.2004.07.079.

  PMID: 15680804 BACKGROUND

• Bernard GR. Acute respiratory distress syndrome: a historical perspective. Am J Respir Crit Care Med. 2005 Oct 1;172(7):798-806. doi: 10.1164/rccm.200504-663OE. Epub 2005 Jul 14.

  PMID: 16020801 BACKGROUND

• Annane D, Sebille V, Bellissant E; Ger-Inf-05 Study Group. Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome. Crit Care Med. 2006 Jan;34(1):22-30. doi: 10.1097/01.ccm.0000194723.78632.62.

  PMID: 16374152 BACKGROUND

• Beiderlinden M, Eikermann M, Boes T, Breitfeld C, Peters J. Treatment of severe acute respiratory distress syndrome: role of extracorporeal gas exchange. Intensive Care Med. 2006 Oct;32(10):1627-31. doi: 10.1007/s00134-006-0262-y. Epub 2006 Jul 28.

  PMID: 16874497 BACKGROUND

MeSH Terms

Conditions

Respiratory Distress Syndrome; Multiple Organ Failure

Interventions

hydrocortisone hemisuccinate; Methylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Pei-Ming Huang, MD, MS

  National Taiwan University Hospital and National Taiwan University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2011
• First Posted: August 26, 2011
• Study Start: June 1, 2005
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: August 26, 2011

Record last verified: 2011-08

Locations

TW (1)