Anemia, Sickle CellPhase 2NCT00094887
Nitric Oxide Inhalation to Treat Sickle Cell Pain Crises
A Phase 2 study testing Nitric Oxide in people with Anemia, Sickle Cell, run by Mallinckrodt at 11 sites in United States.
Trial summary
This study will examine whether nitric oxide (NO) gas can reduce the time it takes for pain to go away in patients who are in sickle cell crisis. NO is important in regulating blood vessel dilation, and consequently, blood flow. The gas is continuously produced by cells that line the blood vessels. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Anemia, Sickle Cell
- What is being tested?
- Nitric Oxide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 11 sitesUnited States
- Study dates
- Oct 2004to Dec 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Each subject must meet all of the following inclusion criteria during the screening process in order to participate in the study:
- Patient must have a diagnosis of SCD (known SS, S-Beta-thalassemia or other hemoglobinopathies causing sickle cell disease). Patients with disease due to Hgb SC are not permitted.
- Must present to the ED/EC or other appropriate unit in VOC.
- Greater than or equal to 10 years old.
- Written informed consent/assent has been obtained.
Who cannot join
- Subjects meeting any of the following criteria during baseline evaluation will be excluded from entry into the study:
- Exposure to therapeutic nitric oxide within the past 12 hours.
- Patient has received sildenafil or other phosphodiesterase 5 inhibitors, therapeutic L-arginine, nitroprusside or nitroglycerine within the past 12 hours.
- Patient has received previous ED/EC or other appropriate unit treatment for a vaso-occlusive crisis less than 48 hours or hospitalization less than 14 days ago (patients transferred directly from another ED or clinic may be enrolled).
- Patient has visited the ED/EC or other appropriate unit greater than 10 times in the past year having a vaso-occlusive crisis.
- Patients presenting with clinically diagnosed bacterial infection (e.g., osteomyelitis, pneumonia, sepsis or meningitis).
Show all 12Show fewer
- Patients who are currently enrolled in any other investigational drug study except for hydroxyurea studies.
- Pregnant women (urine HCG + )/ nursing mothers.
- Patients who have received an exchange transfusion (not simple transfusion) in the last 30 days or are on a chronic simple or exchange transfusion program.
- Suspected splenic sequestration.
- Acute chest syndrome or pneumonia: Abnormal new pulmonary infiltrate (alveolar infiltration and not atelectasis) and one or more pulmonary signs and/or symptoms (fever, rales, wheezing, cough, shortness of breath, retractions).
- Previous participation in this study.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Colorado Sickle Cell Treatement and Research Center
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21205
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
University of Alabama
Birmingham, Alabama, 35294
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Childrens Hospital, Boston
Boston, Massachusetts, 02115
Case Western Reserve University Hospital
Cleveland, Ohio, 44106-2602
Children's Hospital Oakland
Oakland, California, 94609-1809
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Childrens Hospital, Pittsburgh
Pittsburgh, Pennsylvania, 15213-2583
Howard University Hospital
Washington D.C., District of Columbia, 20060
About this study
Official title: A Prospective, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis
This study will examine whether nitric oxide (NO) gas can reduce the time it takes for pain to go away in patients who are in sickle cell crisis. NO is important in regulating blood vessel dilation, and consequently, blood flow. The gas is continuously produced by cells that line the blood vessels. It is also transported from the lungs by hemoglobin in red blood cells.
Patients 10 years of age or older with sickle cell disease (known SS, S-beta-thalassemia or other blood problems causing sickle cell disease) may be eligible for this study. Patients whose disease is due to hemoglobin (Hgb) SC are excluded. Candidates are screened with blood tests and a chest x-ray to look at the lungs and heart.
Read more
Participants are admitted to the hospital in a pain crisis. They are evaluated and then randomly assigned to receive one of two treatments: 1) standard treatment plus NO, or 2) standard treatment plus placebo. The placebo used in this study is nitrogen, a gas that makes up most of the air we breathe and is not known to help in sickle cell disease.
For the first 8 hours of the study, patients receive placebo or NO through a facemask. The mask may be taken off for 5 minutes every hour and for not more than 20 minutes to eat a meal. After the first 8 hours, the gas is delivered through a nasal cannula (small plastic tubing that rests under the nose) that may be taken off only while showering or using the restroom. Patients are questioned about the severity of their pain when they start the study and then every few hours while they are in the hospital. Their vital signs (temperature, breathing rate, and blood pressure) and medicines are checked. Patients will breathe the gas for a maximum of 3 days, but will stay hospitalized until the patient feels well enough to go home. Patients are followed up about 1 month after starting the study by a return visit to the hospital or by a phone call.
Read the detailed description
The object of this study is to determine the safety and efficacy of nitric oxide for inhalation in the treatment of vaso-occlusive pain crisis (VOC) in patients with sickle cell disease. The study population will include patients with sickle cell disease (SS, S-beta-Thalassemia) presenting with vaso-occlusive pain crisis. Patients will be administered either placebo or inhaled nitric oxide to see if the experimental agent, inhaled nitric oxide, can reduce the time it takes for resolution of the vaso-occlusive crisis.
- Conditions
- Anemia, Sickle Cell
- Being tested
- Nitric Oxide, Placebo
- Keywords
- Blood Flow, Nitric Oxide, Pain Crisis, Sickle Cell Anemia, Vaso-Occlusive Crisis, Sickle Cell Disease, SCD
- Medical subject headings
- Anemia, Sickle Cell, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
Also called INOmax
Nitric oxide will be delivered for 4 hours at 80 ppm through a face mask. The dose will then be reduced to 40 ppm for 4 hours. After a total of 8 hours of treatment through face mask, the patient will get 6 mL/puls/breath of NO at 800 ppm or 3 m//pulse/breath, depending on patient weight.
PlaceboDrug
Nitrogen gas will be delivered in the same manor as the experimental drug.
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Nitric Oxide | Experimental | Participants receive Inhaled nitric oxide (INO) Receives: Drug: Nitric Oxide |
| Placebo | Placebo comparator | Participants receive Nitrogen gas Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Vaso-occlusive Pain Crisis (VOC) Resolution
VOC resolution was defined by all of the following conditions:
- Pain relief - Visual Analog Scale (VAS) pain scores of 6 or less, (6 as worst and 0 as best)
- Freedom from parenteral narcotic use,
- Ability to walk unless the subject was not able to walk for any reason other than acute VOC prior to the onset of crisis,
- Subject and/or family's belief that the painful crisis could be managed at home with or without oral analgesic use, and the physician concurred with that assessment.
Measured: within 30 days
Secondary outcomes (5)
Length of Hospitalization
Length of hospitalization is defined as the length of time from admission to discharge order
Measured: within 40 days
Number of Participants Discharged to Home Within the First 24 Hours
Measured: within 24 hours
Total Dose of Opioids Received
The total dose (mg) of opioid medications received during the trial
Measured: within 8 hours and within 40 days
Number of Participants With Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion
Number of participants who required a blood transfusion before discharge because of acute chest syndrome/pneumonia
Measured: within 40 days
Number of Participants Readmitted to Hospital Within 30 Days After Discharge
The number of participants readmitted to the hospital for any reason within 30 days after discharge
Measured: during first 24 hours and during 30 day follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2004 (estimated)
- Study startOct 2004
- Primary completionDec 2008
- Study completionDec 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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Anemia, Sickle CellStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mallinckrodt
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- James Baldassarre, MD, Study director, Mallinckrodt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00094887
- Sponsor's protocol ID
- INOT 36
- Other IDs
- 05-H-0019
- Status last verified
- Oct 2017
- First submitted
- 28 Oct 2004
- Last updated
- 5 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Sanders DY, Severance HW, Pollack CV Jr. Sickle cell vaso-occlusive pain crisis in adults: alternative strategies for management in the emergency department. South Med J. 1992 Aug;85(8):808-11. doi: 10.1097/00007611-199208000-00005.
PubMed 1302470Gladwin MT, Kato GJ, Weiner D, Onyekwere OC, Dampier C, Hsu L, Hagar RW, Howard T, Nuss R, Okam MM, Tremonti CK, Berman B, Villella A, Krishnamurti L, Lanzkron S, Castro O, Gordeuk VR, Coles WA, Peters-Lawrence M, Nichols J, Hall MK, Hildesheim M, Blackwelder WC, Baldassarre J, Casella JF; DeNOVO Investigators. Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA. 2011 Mar 2;305(9):893-902. doi: 10.1001/jama.2011.235.
PubMed 21364138
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis
- ClinicalTrials.gov ID
- NCT00094887
- Acronym / sponsor ID
- INOT 36
- Conditions
- Anemia, Sickle Cell
- Keywords
- Blood Flow, Nitric Oxide, Pain Crisis, Sickle Cell Anemia, Vaso-Occlusive Crisis, Sickle Cell Disease, SCD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- MallinckrodtIndustry (pharma, biotech, devices)
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Oct 2004
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 28 Oct 2004 (estimated)
- Results
- Posted 23 Apr 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine whether nitric oxide (NO) gas can reduce the time it takes for pain to go away in patients who are in sickle cell crisis. NO is important in regulating blood vessel dilation, and consequently, blood flow. The gas is continuously produced by cells that line the blood vessels. It is also transported from the lungs by hemoglobin in red blood cells.
Patients 10 years of age or older with sickle cell disease (known SS, S-beta-thalassemia or other blood problems causing sickle cell disease) may be eligible for this study. Patients whose disease is due to hemoglobin (Hgb) SC are excluded. Candidates are screened with blood tests and a chest x-ray to look at the lungs and heart.
Participants are admitted to the hospital in a pain crisis. They are evaluated and then randomly assigned to receive one of two treatments: 1) standard treatment plus NO, or 2) standard treatment plus placebo. The placebo used in this study is nitrogen, a gas that makes up most of the air we breathe and is not known to help in sickle cell disease.
For the first 8 hours of the study, patients receive placebo or NO through a facemask. The mask may be taken off for 5 minutes every hour and for not more than 20 minutes to eat a meal. After the first 8 hours, the gas is delivered through a nasal cannula (small plastic tubing that rests under the nose) that may be taken off only while showering or using the restroom. Patients are questioned about the severity of their pain when they start the study and then every few hours while they are in the hospital. Their vital signs (temperature, breathing rate, and blood pressure) and medicines are checked. Patients will breathe the gas for a maximum of 3 days, but will stay hospitalized until the patient feels well enough to go home. Patients are followed up about 1 month after starting the study by a return visit to the hospital or by a phone call.
Detailed description
The object of this study is to determine the safety and efficacy of nitric oxide for inhalation in the treatment of vaso-occlusive pain crisis (VOC) in patients with sickle cell disease. The study population will include patients with sickle cell disease (SS, S-beta-Thalassemia) presenting with vaso-occlusive pain crisis. Patients will be administered either placebo or inhaled nitric oxide to see if the experimental agent, inhaled nitric oxide, can reduce the time it takes for resolution of the vaso-occlusive crisis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled Nitric Oxide | Experimental | Drug: Nitric OxideParticipants receive Inhaled nitric oxide (INO) |
| Placebo | Placebo comparator | Drug: PlaceboParticipants receive Nitrogen gas |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Each subject must meet all of the following inclusion criteria during the screening process in order to participate in the study:
- Patient must have a diagnosis of SCD (known SS, S-Beta-thalassemia or other hemoglobinopathies causing sickle cell disease). Patients with disease due to Hgb SC are not permitted.
- Must present to the ED/EC or other appropriate unit in VOC.
- Greater than or equal to 10 years old.
- Written informed consent/assent has been obtained.
Key exclusion criteria (12 listed)
- Subjects meeting any of the following criteria during baseline evaluation will be excluded from entry into the study:
- Exposure to therapeutic nitric oxide within the past 12 hours.
- Patient has received sildenafil or other phosphodiesterase 5 inhibitors, therapeutic L-arginine, nitroprusside or nitroglycerine within the past 12 hours.
- Patient has received previous ED/EC or other appropriate unit treatment for a vaso-occlusive crisis less than 48 hours or hospitalization less than 14 days ago (patients transferred directly from another ED or clinic may be enrolled).
- Patient has visited the ED/EC or other appropriate unit greater than 10 times in the past year having a vaso-occlusive crisis.
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: INOmaxNitric oxide will be delivered for 4 hours at 80 ppm through a face mask. The dose will then be reduced to 40 ppm for 4 hours. After a total of 8 hours of treatment through face mask, the patient will get 6 mL/puls/breath of NO at 800 ppm or 3 m//pulse/breath, depending on patient weight. | Drug | Inhaled Nitric Oxide |
| PlaceboNitrogen gas will be delivered in the same manor as the experimental drug. | Drug | Placebo |
Primary outcome
Time to Vaso-occlusive Pain Crisis (VOC) Resolution
Time frame: within 30 days
VOC resolution was defined by all of the following conditions: * Pain relief - Visual Analog Scale (VAS) pain scores of 6 or less, (6 as worst and 0 as best) * Freedom from parenteral narcotic use, * Ability to walk unless the subject was not able to walk for any reason other than acute VOC prior to the onset of crisis, * Subject and/or family's belief that the painful crisis could be managed at home with or without oral analgesic use, and the physician concurred with that assessment.
5 secondary outcomes
Length of Hospitalization
Time frame: within 40 days
Number of Participants Discharged to Home Within the First 24 Hours
Time frame: within 24 hours
Total Dose of Opioids Received
Time frame: within 8 hours and within 40 days
Number of Participants With Acute Chest Syndrome/Pneumonia Requiring Blood Transfusion
Time frame: within 40 days
Number of Participants Readmitted to Hospital Within 30 Days After Discharge
Time frame: during first 24 hours and during 30 day follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 1302470Sanders DY, Severance HW, Pollack CV Jr. Sickle cell vaso-occlusive pain crisis in adults: alternative strategies for management in the emergency department. South Med J. 1992 Aug;85(8):808-11. doi: 10.1097/00007611-199208000-00005.
- Derived from this study: PubMed 21364138Gladwin MT, Kato GJ, Weiner D, Onyekwere OC, Dampier C, Hsu L, Hagar RW, Howard T, Nuss R, Okam MM, Tremonti CK, Berman B, Villella A, Krishnamurti L, Lanzkron S, Castro O, Gordeuk VR, Coles WA, Peters-Lawrence M, Nichols J, Hall MK, Hildesheim M, Blackwelder WC, Baldassarre J, Casella JF; DeNOVO Investigators. Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial. JAMA. 2011 Mar 2;305(9):893-902. doi: 10.1001/jama.2011.235.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
James Baldassarre, MD study director
Mallinckrodt
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitric Oxide in people with Anemia, Sickle Cell, run by Mallinckrodt at 11 sites in United States.
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 5 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 5 Feb 2020. 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. 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 23 Apr 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?
Time to Vaso-occlusive Pain Crisis (VOC) Resolution (time frame: within 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 NCT00094887, which also lists 2 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 5 Feb 2020.