Extracorporeal Carbon Dioxide Removal for Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome Clinical Trial

Official title:

Extracorporeal Carbon Dioxide Removal for Acute Respiratory Distress Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000572
• Other study ID #: 210
• Secondary ID: R01HL036787
• Status: Completed
• Phase: Phase 3
• First received: October 27, 1999
• Last updated: March 4, 2018
• Start date: June 1987
• Est. completion date: January 1993

Study information

• Verified date: March 2018
• Source: Intermountain Health Care, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare conventional therapy using low frequency positive pressure ventilation with extracorporeal CO2 removal for the treatment of adult respiratory distress syndrome (ARDS).

Description:

BACKGROUND:

It is estimated that at least 150,000 individuals die each year of adult respiratory distress syndrome. Treatment remains largely supportive. The National Heart, Lung, and Blood Institute (NHLBI) conducted the Extracorporeal Support for Respiratory Insufficiency (ECMO, Extracorporeal Membrane Oxygenation) trial from June 1974 through 1978. In ECMO, 90 patients were randomized to either extracorporeal membrane oxygenation plus conventional therapy or to conventional therapy. Survival rates were less than ten percent in both groups. The failure of the trial to demonstrate the superiority of ECMO over conventional ventilatory support resulted in the virtual elimination of the use of ECMO in clinical medicine.

In the earlier NHLBI trial, ECMO was implemented with a veno-arterial shunt which approximated 90 percent of the baseline cardiac output. Ventilation of the lungs was continued with reduced function of inspiration oxygen. Thus, the lungs were deprived of the principle source of blood supply while continuously exposed to potentially injurious ventilatory pressures and gas composition. The present patient trial used a new form of therapy developed by Dr. Gattinoni and co-workers in Milan, Italy with the collaboration of Dr. Kolobow at the National Institutes of Health in Bethesda. The authors reported a 77 percent survival rate for the new therapy. In Step 1 of the new therapy, the patient was initially ventilated with pressure-controlled, inverted ratio ventilation. If the patient did not improve, Step 2 using extracorporeal perfusion was performed with a veno-venous shunt in contrast to a veno-arterial shunt. The veno-venous shunt preserved pulmonary blood flow whereas the veno-arterial shunt diminished it. Step 3 was reserved for those patients who did not meet the therapeutic criteria of Step 2. They underwent low frequency positive-pressure ventilation and extracorporeal CO2 removal involving veno-venous bypass via the internal jugular and femoral or bilateral saphenous veins.

DESIGN NARRATIVE:

Randomized, fixed sample. Patients were stratified by age (under and over 40 years) and by the presence or absence of trauma. Patients were assigned to conventional positive pressure ventilation therapy or to a three-step therapeutic program employing pressure-controlled-inverted-ratio-ventilation, continuous positive airway pressure, and low-frequency positive pressure ventilation-extracorporeal CO2 removal. The main outcome measure was survival at 30 days after randomization. Secondary outcome measures included hospital costs, physiologic data, length of hospital stay, and blood product consumption. Follow-up took place during the year after hospital discharge.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 1993
• Est. primary completion date: April 1991
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Men and women with acute respiratory distress syndrome.

Inclusion Criteria: ECMO ENTRY CRITERIA (PaO2 < 50 mm Hg -REPEATED THREE TIMES):

Rapid entry: 2 hours at fraFIO2=1.00 and PEEP>5 cm H2O with PaCO2=30-45 mmHg

Slow entry: 12 hours at fraction of inspired oxygen (FIO2)>0.60 and positive end-expiratory pressure (PEEP)>5 cm H2O with PaCO2=30-45 mmHg and right to Left shunt fraction >0.30

Exclusion Criteria:

1. Contraindication to anti-coagulation (for example, gastrointestinal bleeding, recent cerebrovascular accident, or chronic bleeding disorder).

2. Pw > 25 mm Hg (superseded by our screening criterion that Pw ~ 15 mm Hg).

3. Mechanical ventilation >21. days.

4. Severe chronic systemic disease or another clinical condition that, in itself,greatly limits survival; for example,

1. Irreversible central nervous system disease

2. Severe chronic pulmonary disease (forced expiratory volume in 1 second (FEV1)<1 L, FEV1/FVC(forced vital capacity) <0.3 of predicted, chronic PaCO2 >45 mm Hg, chest x-ray evidence of overinflation or interstitial infiltration, or previous hospitalization for chronic respiratory insufficiency)

3. Total-body surface burns> 40%

4. Rapidly fatal malignancy

5. Chronic left ventricular failure

6. Chronic renal failure (we required serum creatlnlne ~ 2 mg/dl or chronic dialysis therapy)

7. Chronic liver failure (we required total serum bilirubin;?; 2 mg/dl)

8. Immunosuppressed patients and patients with a positive human immu.. nodeficiency virus test

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Lung Diseases
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Procedure:
• positive-pressure ventilation
Detailed computer protocol controlled positive pressure ventilation
• extracorporeal membrane oxygenation (CO2 removal)
Detailed computer protocol controlled Extracorporeal CO2 Removal with reduced positive pressure ventilation

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Intermountain Health Care, Inc.	National Heart, Lung, and Blood Institute (NHLBI)

References & Publications (19)

Brunet F, Mira JP, Dhainaut JF, Dall'ava-Santucci J. Efficacy of low-frequency positive-pressure ventilation-extracorporeal CO2 removal. Am J Respir Crit Care Med. 1995 Apr;151(4):1269-70. — View Citation

East TD, Böhm SH, Wallace CJ, Clemmer TP, Weaver LK, Orme JF Jr, Morris AH. A successful computerized protocol for clinical management of pressure control inverse ratio ventilation in ARDS patients. Chest. 1992 Mar;101(3):697-710. — View Citation

East TD, Morris AH, Wallace CJ, Clemmer TP, Orme JF Jr, Weaver LK, Henderson S, Sittig DF. A strategy for development of computerized critical care decision support systems. Int J Clin Monit Comput. 1991-1992;8(4):263-9. — View Citation

Falke KJ. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):1016-7. — View Citation

Habashi NM, Reynolds HN, Borg U, Cowley RA. Randomized clinical trial of pressure-controlled inverse ration ventilation and extra corporeal CO2 removal for ARDS. Am J Respir Crit Care Med. 1995 Jan;151(1):255-6. — View Citation

Henderson S, Crapo RO, Wallace CJ, East TD, Morris AH, Gardner RM. Performance of computerized protocols for the management of arterial oxygenation in an intensive care unit. Int J Clin Monit Comput. 1991-1992;8(4):271-80. — View Citation

Morris AH, East TD, Wallace CJ, Orme J Jr, Clemmer T, Weaver L, Thomas F, Dean N, Pearl J, Rasmusson B. Ethical implications of standardization of ICU care with computerized protocols. Proc Annu Symp Comput Appl Med Care. 1994:501-5. — View Citation

Morris AH, Menlove RL, Rollins RJ, Wallace CJ, Beck E. A controlled clinical trial of a new 3-step therapy that includes extracorporeal CO2 removal for ARDS. ASAIO Trans. 1988 Jan-Mar;34(1):48-53. — View Citation

Morris AH, Wallace CJ, Menlove RL, Clemmer TP, Orme JF Jr, Weaver LK, Dean NC, Thomas F, East TD, Pace NL, Suchyta MR, Beck E, Bombino M, Sittig DF, Böhm S, Hoffmann B, Becks H, Butler S, Pearl J, Rasmusson B. Randomized clinical trial of pressure-control — View Citation

Morris AH. Adult respiratory distress syndrome and new modes of mechanical ventilation: reducing the complications of high volume and high pressure. New Horiz. 1994 Feb;2(1):19-33. Review. — View Citation

Morris AH. Protocol management of adult respiratory distress syndrome. New Horiz. 1993 Nov;1(4):593-602. Review. Erratum in: New Horiz 1994 Feb;2(1):7. — View Citation

Morris AH. Uncertainty in the management of ARDS: lessons for the evaluation of a new therapy. Intensive Care Med. 1994;20(2):87-9. — View Citation

Sittig DF, Gardner RM, Morris AH, Wallace CJ. Clinical evaluation of computer-based respiratory care algorithms. Int J Clin Monit Comput. 1990 Jul;7(3):177-85. — View Citation

Sittig DF, Gardner RM, Pace NL, Morris AH, Beck E. Computerized management of patient care in a complex, controlled clinical trial in the intensive care unit. Comput Methods Programs Biomed. 1989 Oct-Nov;30(2-3):77-84. — View Citation

Sittig DF, Pace NL, Gardner RM, Beck E, Morris AH. Implementation of a computerized patient advice system using the HELP clinical information system. Comput Biomed Res. 1989 Oct;22(5):474-87. — View Citation

Suchyta MR, Clemmer TP, Elliott CG, Orme JF Jr, Weaver LK. The adult respiratory distress syndrome. A report of survival and modifying factors. Chest. 1992 Apr;101(4):1074-9. — View Citation

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. — View Citation

Suchyta MR, Elliott CG, Colby T, Rasmusson BY, Morris AH, Jensen RL. Open lung biopsy does not correlate with pulmonary function after the adult respiratory distress syndrome. Chest. 1991 May;99(5):1232-7. — View Citation

Suchyta MR, Elliott CG, Jensen RL, Crapo RO. Predicting the presence of pulmonary function impairment in adult respiratory distress syndrome survivors. Respiration. 1993;60(2):103-8. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hospital costs	$US	Hospital stay
Other	Bleeding/Hemorrhage	Bleeding in ECCO2R subjects exceeded that in control subjects	Hospital stay
Primary	Survival	All deaths occurred within 30 days of enrollment	Hospital stay (time until death): participants will be followed for the duration of hospital stay, an expected average of 30 days).
Secondary	Hospital days		up to hospital discharge, approximately 30 days
Secondary	ICU days		up to ICU discharge, approximately 30 days