Acute Respiratory Distress SyndromePhase 3NCT00000572
Extracorporeal Carbon Dioxide Removal for Acute Respiratory Distress Syndrome
A Phase 3 study testing positive-pressure ventilation and extracorporeal membrane oxygenation (CO2 removal) in people with Acute Respiratory Distress Syndrome and Lung Diseases, run by Intermountain Health Care, Inc..
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Lung Diseases
- What is being tested?
- positive-pressure ventilation and extracorporeal membrane oxygenation (CO2 removal)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Jun 1987to Jan 1993
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Contraindication to anti-coagulation (for example, gastrointestinal bleeding, recent cerebrovascular accident, or chronic bleeding disorder).
- Pw > 25 mm Hg (superseded by our screening criterion that Pw ~ 15 mm Hg).
- Mechanical ventilation >21. days.
- Severe chronic systemic disease or another clinical condition that, in itself,greatly limits survival; for example,
- Irreversible central nervous system disease
- 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)
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- Total-body surface burns> 40%
- Rapidly fatal malignancy
- Chronic left ventricular failure
- Chronic renal failure (we required serum creatlnlne ~ 2 mg/dl or chronic dialysis therapy)
- Chronic liver failure (we required total serum bilirubin;?; 2 mg/dl)
- Immunosuppressed patients and patients with a positive human immu.. nodeficiency virus test
About this study
To compare conventional therapy using low frequency positive pressure ventilation with extracorporeal CO2 removal for the treatment of adult respiratory distress syndrome (ARDS).
Read the 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.
- Conditions
- Acute Respiratory Distress Syndrome, Lung Diseases
- Being tested
- positive-pressure ventilation, extracorporeal membrane oxygenation (CO2 removal)
- Medical subject headings
- Respiratory Distress Syndrome, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
positive-pressure ventilationProcedure or surgery
Detailed computer protocol controlled positive pressure ventilation
extracorporeal membrane oxygenation (CO2 removal)Procedure or surgery
Detailed computer protocol controlled Extracorporeal CO2 Removal with reduced positive pressure ventilation
| Study group | Role | What they receive |
|---|---|---|
| Extracorporeal membrane oxygenation (CO2 removal) | Experimental | Detailed Electronic Protocol Controlled Extracorporeal CO2 Removal with reduced positive-pressure ventilation Receives: Procedure: extracorporeal membrane oxygenation (CO2 removal) |
| Protocol Controlled positive-pressure vent | Active comparator | Detailed Electronic Protocol Controlled positive-pressure ventilation Receives: Procedure: positive-pressure ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
All deaths occurred within 30 days of enrollment
Measured: Hospital stay (time until death): participants will be followed for the duration of hospital stay, an expected average of 30 days).
Secondary outcomes (2)
Hospital days
Measured: up to hospital discharge, approximately 30 days
ICU days
Measured: up to ICU discharge, approximately 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 1999 (estimated)
- Study startJun 1987
- Primary completionApr 1991
- Study completionJan 1993
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intermountain Health Care, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Alan H. Morris, Intermountain Health Care, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000572
- Sponsor's protocol ID
- 210
- Other IDs
- R01HL036787
- Status last verified
- Mar 2018
- First submitted
- 27 Oct 1999
- Last updated
- 6 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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. No abstract available.
PubMed 3132189Sittig 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. doi: 10.1016/0169-2607(89)90060-6.
PubMed 2684495Sittig 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. doi: 10.1016/0010-4809(89)90040-2.
PubMed 2776450Sittig 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. doi: 10.1007/BF02915583.
PubMed 2250128Suchyta 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. doi: 10.1378/chest.99.5.1232.
PubMed 2019184Suchyta 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.
PubMed 2009801Henderson 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. doi: 10.1007/BF01739128.
PubMed 1820417East 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. doi: 10.1007/BF01739127.
PubMed 1820416Suchyta 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. doi: 10.1378/chest.101.4.1074.
PubMed 1555423East TD, Bohm 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. doi: 10.1378/chest.101.3.697.
PubMed 1541135Morris 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.
PubMed 7949979Morris 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.
PubMed 7922426Morris AH. Uncertainty in the management of ARDS: lessons for the evaluation of a new therapy. Intensive Care Med. 1994;20(2):87-9. doi: 10.1007/BF01707658. No abstract available.
PubMed 8201102Suchyta 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. doi: 10.1159/000196182.
PubMed 8341851Morris AH. Protocol management of adult respiratory distress syndrome. New Horiz. 1993 Nov;1(4):593-602.
PubMed 8087579
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extracorporeal Carbon Dioxide Removal for Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT00000572
- Acronym / sponsor ID
- 210
- Conditions
- Acute Respiratory Distress Syndrome, Lung Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Intermountain Health Care, Inc.University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jun 1987
- Primary completion
- Apr 1991 (actual)
- Study completion
- Jan 1993 (actual)
- First posted
- 28 Oct 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Extracorporeal membrane oxygenation (CO2 removal) | Experimental | Procedure: extracorporeal membrane oxygenation (CO2 removal)Detailed Electronic Protocol Controlled Extracorporeal CO2 Removal with reduced positive-pressure ventilation |
| Protocol Controlled positive-pressure vent | Active comparator | Procedure: positive-pressure ventilationDetailed Electronic Protocol Controlled positive-pressure ventilation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (12 listed)
- Contraindication to anti-coagulation (for example, gastrointestinal bleeding, recent cerebrovascular accident, or chronic bleeding disorder).
- Pw > 25 mm Hg (superseded by our screening criterion that Pw ~ 15 mm Hg).
- Mechanical ventilation >21. days.
- Severe chronic systemic disease or another clinical condition that, in itself,greatly limits survival; for example,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| positive-pressure ventilationDetailed computer protocol controlled positive pressure ventilation | Procedure or surgery | Protocol Controlled positive-pressure vent |
| extracorporeal membrane oxygenation (CO2 removal)Detailed computer protocol controlled Extracorporeal CO2 Removal with reduced positive pressure ventilation | Procedure or surgery | Extracorporeal membrane oxygenation (CO2 removal) |
Primary outcome
Survival
Time frame: 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
2 secondary outcomes
Hospital days
Time frame: up to hospital discharge, approximately 30 days
ICU days
Time frame: up to ICU discharge, approximately 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2018.
- Background: PubMed 3132189Morris 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. No abstract available.
- Background: PubMed 2684495Sittig 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. doi: 10.1016/0169-2607(89)90060-6.
- Background: PubMed 2776450Sittig 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. doi: 10.1016/0010-4809(89)90040-2.
- Background: PubMed 2250128Sittig 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. doi: 10.1007/BF02915583.
- Background: PubMed 2019184Suchyta 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. doi: 10.1378/chest.99.5.1232.
- Background: PubMed 2009801Suchyta 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.
- Background: PubMed 1820417Henderson 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. doi: 10.1007/BF01739128.
- Background: PubMed 1820416East 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. doi: 10.1007/BF01739127.
- Background: PubMed 1555423Suchyta 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. doi: 10.1378/chest.101.4.1074.
- Background: PubMed 1541135East TD, Bohm 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. doi: 10.1378/chest.101.3.697.
- Background: PubMed 7949979Morris 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.
- Background: PubMed 7922426Morris 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing positive-pressure ventilation and extracorporeal membrane oxygenation (CO2 removal) in people with Acute Respiratory Distress Syndrome and Lung Diseases, run by Intermountain Health Care, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: Hospital stay (time until death): participants will be followed for the duration of hospital stay, an expected average of 30 days).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000572, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2018.