Clinical trial NCT00000572: Extracorporeal Carbon Dioxide Removal for Acute Respiratory Distress Syndrome
Official title: Extracorporeal Carbon Dioxide Removal for Acute Respiratory Distress Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome
Lung Diseases
Lead sponsor: Intermountain Health Care, Inc.
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 1999-10-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival
timeFrame: Hospital stay (time until death): participants will be followed for the duration of hospital stay, an expected average of 30 days).
Secondary outcomes:
measure: Hospital days
timeFrame: up to hospital discharge, approximately 30 days
measure: ICU days
timeFrame: up to ICU discharge, approximately 30 days
Other outcomes:
measure: Hospital costs
timeFrame: Hospital stay
measure: Bleeding/Hemorrhage
timeFrame: Hospital stay
Locations:
Study officials:
References:
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