Congestive Heart FailurePhase 2NCT00060840
The Effects of Nitric Oxide for Inhalation During Left Ventricular Assists Device (LVAD) Implantation
A Phase 2 study testing Nitric Oxide and Nitrogen in people with Congestive Heart Failure, run by Mallinckrodt at 11 sites in 3 countries.
Trial summary
The purpose of this study is to assess the utility of nitric oxide for inhalation during left ventricular assist device (LVAD) implantation following cardiopulmonary bypass (CPB). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congestive Heart Failure
- What is being tested?
- Nitric Oxide and Nitrogen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 11 sitesin 3 countries
- Study dates
- Jul 2003to Jul 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled to undergo their first LVAD implantation, (or at least 6 months after explanation of a previous LVAD).
- Has a pulmonary vascular resistance of at least 2.5 Wood units (200 dynes/sec.) in the 30 days prior to LVAD placement.
- Greater than 18 years of age.
- Signed IRB approved informed consent.
Who cannot join
- Patients with congestive heart failure due to giant cell myocarditis or restrictive cardiomyopathy.
- Elective Biventricular Assist Device (BiVAD) surgery, or current support with a temporary BiVad.
- LVAD procedure expected to be done without cardiopulmonary bypass.
- Pregnancy (a negative pregnancy test must be documented prior to enrollment).
- Received nitric oxide by inhalation therapy within the past 24 hours.
- Investigational drugs that are expected to change systemic or pulmonary vascular resistance are not allowed.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States8 sites
University of Cincinnati
Cincinnati, Ohio, 45219
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Baylor University Medical Center
Dallas, Texas, 75226
University of Texas/St. Paul Medical Center
Dallas, Texas, 75390
Duke University Medical Center
Durham, North Carolina, 27710
Texas Heart Institute
Houston, Texas, 20345
Newark Beth Isreal Medical Center
Newark, New Jersey, 07112
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Germany2 sites
Deutsches Herfzzentrum Berlin
Augustenburger Platz, State of Berlin, 13353
Herz-und Diabeteszentrum Nordrhein-Westfalen
Gergstrab, Bad Oeynhausen, 32545
About this study
Official title: The Effects of Nitric Oxide for Inhalation During Left Ventricular Assist Device (LVAD) Implantation
The purpose of this study is to assess the utility of nitric oxide for inhalation during left ventricular assist device (LVAD) implantation following cardiopulmonary bypass (CPB). This is to be assessed by the number of patients in each treatment group meeting failure criteria within 24 hours on study drug, as defined by two or more of the following:
- Left ventricular flow rate index (LVFRI) ≤ 2.0 L/min/m^2
- Administration of ≥ 20 inotropic equivalents (IE)
- 10 µg/kg/min dopamine, dobutamine, enoximone or amrinone is equivalent to 10 IE
- 0.1 µg/kg/min epinephrine or norepinephrine is equivalent to 10 IE
- 1 µg/kg/min milrinone is equivalent to 15 IE
- 0.1 U/min vasopressin is equivalent to 10 IE
- Mean arterial pressure (MAP) ≤ 55 mmHg
- Central venous pressure (CVP) ≥ 16 mmHg
- Percent mixed venous oxygen saturation (SvO2) ≤ 55%
Read more
Or at least one of the following criteria:
- Failure to wean from cardiopulmonary bypass at least once due to hemodynamic failure. Re-initiation of cardiopulmonary bypass to correct bleeding or other technical issues will not be considere 'failure to wean'
- Death
Read the detailed description
40 ppm of either nitric oxide for inhalation or N2 (placebo) will be continuously administered to the patient starting at least 5 minutes prior to initiating the first weaning attempt from CPB and continue until the patient is either extubated, has reached failure criteria, or has been treated with study drug for 48 hours following discontinuation of CPB, whichever come first.
All patients will be monitored peri-operatively with a pulmonary arterial line, central venous line, and systemic arterial line. Baseline data collection by a designated clinical staff member will begin following induction of anesthesia and prior to skin incision. Following a successful wean from cardiopulmonary bypass, post-op data will be collected within 1 hour following end time of surgery. Data will then be collected at 6, 12, 18, 24, and 48 hours from post-op or until extubation, in which case weaning from study drug will begin.
Open label investigational nitric oxide for inhalation may be administered once a patient meets a minimum of two of the failure criteria or fails to wean at least once due to hemodynamic failure from cardiopulmonary bypass.
- Conditions
- Congestive Heart Failure
- Being tested
- Nitric Oxide, Nitrogen
- Keywords
- Left Ventricular Assist Device Implantation, Progressive Left Ventricular Failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
Also called INOmax
40 ppm of Nitric Oxide continuously administered for 48 hours
NitrogenDrug
Nitrogen (N2) administered at 40 ppm for 48 hours
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Nitric Oxide | Active comparator | Inhaled Nitric Oxide (iNO) at 40 parts per million (ppm) Receives: Drug: Nitric Oxide |
| Nitrogen | Placebo comparator | Nitrogen (N2) administered at 40 ppm. Receives: Drug: Nitrogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Subjects With Left Ventricular Failure During Left Ventricular Assistance Device (LVAD) Placement After Cardio Pulmonary Bypass, as Determined by Failure Criteria, After Administration of Nitric Oxide.
Failure criteria used to measure outcome includes:
- Left ventricular flow rate index (LVFRI) ≤ 2.0 L/min/m^2
- Administration of ≥ 20 inotropic equivalents (IE)
- Mean arterial pressure (MAP) ≤ 55 mm Hg
- Central venous pressure (CVP) ≥ 16 mm Hg
- Percentage of mixed venous oxygen saturation (SvO2) of ≤ 55% OR failure to wean from cardio pulmonary bypass (CPB) at least once due to hemodynamic failure or death.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2003 (estimated)
- Study startJul 2003
- Primary completionJun 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Congestive Heart FailureStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mallinckrodt
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Baldassarre, MD, Study director, Mallinckrodt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00060840
- Sponsor's protocol ID
- INOT 41
- Status last verified
- Jul 2016
- First submitted
- 14 May 2003
- Last updated
- 22 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Nitric Oxide for Inhalation During Left Ventricular Assist Device (LVAD) Implantation
- ClinicalTrials.gov ID
- NCT00060840
- Acronym / sponsor ID
- INOT 41
- Conditions
- Congestive Heart Failure
- Keywords
- Left Ventricular Assist Device Implantation, Progressive Left Ventricular Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- MallinckrodtIndustry (pharma, biotech, devices)
- Study start
- Jul 2003
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 15 May 2003 (estimated)
- Results
- Posted 17 Sep 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the utility of nitric oxide for inhalation during left ventricular assist device (LVAD) implantation following cardiopulmonary bypass (CPB). This is to be assessed by the number of patients in each treatment group meeting failure criteria within 24 hours on study drug, as defined by two or more of the following:
- Left ventricular flow rate index (LVFRI) ≤ 2.0 L/min/m^2
- Administration of ≥ 20 inotropic equivalents (IE)
- 10 µg/kg/min dopamine, dobutamine, enoximone or amrinone is equivalent to 10 IE
- 0.1 µg/kg/min epinephrine or norepinephrine is equivalent to 10 IE
- 1 µg/kg/min milrinone is equivalent to 15 IE
- 0.1 U/min vasopressin is equivalent to 10 IE
- Mean arterial pressure (MAP) ≤ 55 mmHg
- Central venous pressure (CVP) ≥ 16 mmHg
- Percent mixed venous oxygen saturation (SvO2) ≤ 55%
Or at least one of the following criteria:
- Failure to wean from cardiopulmonary bypass at least once due to hemodynamic failure. Re-initiation of cardiopulmonary bypass to correct bleeding or other technical issues will not be considere 'failure to wean'
- Death
Detailed description
40 ppm of either nitric oxide for inhalation or N2 (placebo) will be continuously administered to the patient starting at least 5 minutes prior to initiating the first weaning attempt from CPB and continue until the patient is either extubated, has reached failure criteria, or has been treated with study drug for 48 hours following discontinuation of CPB, whichever come first.
All patients will be monitored peri-operatively with a pulmonary arterial line, central venous line, and systemic arterial line. Baseline data collection by a designated clinical staff member will begin following induction of anesthesia and prior to skin incision. Following a successful wean from cardiopulmonary bypass, post-op data will be collected within 1 hour following end time of surgery. Data will then be collected at 6, 12, 18, 24, and 48 hours from post-op or until extubation, in which case weaning from study drug will begin.
Open label investigational nitric oxide for inhalation may be administered once a patient meets a minimum of two of the failure criteria or fails to wean at least once due to hemodynamic failure from cardiopulmonary bypass.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled Nitric Oxide | Active comparator | Drug: Nitric OxideInhaled Nitric Oxide (iNO) at 40 parts per million (ppm) |
| Nitrogen | Placebo comparator | Drug: NitrogenNitrogen (N2) administered at 40 ppm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Scheduled to undergo their first LVAD implantation, (or at least 6 months after explanation of a previous LVAD).
- Has a pulmonary vascular resistance of at least 2.5 Wood units (200 dynes/sec.) in the 30 days prior to LVAD placement.
- Greater than 18 years of age.
- Signed IRB approved informed consent.
Key exclusion criteria (6 listed)
- Patients with congestive heart failure due to giant cell myocarditis or restrictive cardiomyopathy.
- Elective Biventricular Assist Device (BiVAD) surgery, or current support with a temporary BiVad.
- LVAD procedure expected to be done without cardiopulmonary bypass.
- Pregnancy (a negative pregnancy test must be documented prior to enrollment).
- Received nitric oxide by inhalation therapy within the past 24 hours.
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 |
|---|---|---|
| Nitric OxideAlso: INOmax40 ppm of Nitric Oxide continuously administered for 48 hours | Drug | Inhaled Nitric Oxide |
| NitrogenNitrogen (N2) administered at 40 ppm for 48 hours | Drug | Nitrogen |
Primary outcome
The Number of Subjects With Left Ventricular Failure During Left Ventricular Assistance Device (LVAD) Placement After Cardio Pulmonary Bypass, as Determined by Failure Criteria, After Administration of Nitric Oxide.
Time frame: 28 days
Failure criteria used to measure outcome includes: * Left ventricular flow rate index (LVFRI) ≤ 2.0 L/min/m^2 * Administration of ≥ 20 inotropic equivalents (IE) * Mean arterial pressure (MAP) ≤ 55 mm Hg * Central venous pressure (CVP) ≥ 16 mm Hg * Percentage of mixed venous oxygen saturation (SvO2) of ≤ 55% OR failure to wean from cardio pulmonary bypass (CPB) at least once due to hemodynamic failure or death.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Congestive Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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.
James Baldassarre, MD study director
Mallinckrodt
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitric Oxide and Nitrogen in people with Congestive Heart Failure, run by Mallinckrodt at 11 sites in 3 countries.
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 4 inclusion and 6 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 22 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Sep 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Number of Subjects With Left Ventricular Failure During Left Ventricular Assistance Device (LVAD) Placement After Cardio Pulmonary Bypass, as Determined by Failure Criteria, After Administration of Nitric Oxide. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Aug 2016.