Extracorporeal Carbon Dioxide Removal for Acute Respiratory Distress Syndrome

Phase 3

Completed

• Conditions: Acute Respiratory Distress Syndrome; Lung Diseases
• Interventions: Procedure: extracorporeal membrane oxygenation (CO2 removal); Procedure: positive-pressure ventilation

• Registration Number: NCT00000572
• Lead Sponsor: Intermountain Health Care, Inc.

Brief Summary

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

Detailed 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.

Study Timeline

• Study Start: 1987-06
• Primary Completion: 1991-04
• Study Completion: 1993-01
• Study First Submitted: 1999-10-27
• Study First Submitted QC: 1999-10-27
• Study First Posted: 1999-10-28
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-04
• Last Update Posted: 2018-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Extracorporeal membrane oxygenation (CO2 removal)	extracorporeal membrane oxygenation (CO2 removal)	Detailed Electronic Protocol Controlled Extracorporeal CO2 Removal with reduced positive-pressure ventilation
Protocol Controlled positive-pressure vent	positive-pressure ventilation	Detailed Electronic Protocol Controlled positive-pressure ventilation

Primary Outcome Measures

Name	Time	Method
Survival	Hospital stay (time until death): participants will be followed for the duration of hospital stay, an expected average of 30 days).	All deaths occurred within 30 days of enrollment

Secondary Outcome Measures

Name	Time	Method
Hospital days	up to hospital discharge, approximately 30 days
ICU days	up to ICU discharge, approximately 30 days