Sickle Cell DiseasePhase 2NCT00142051
Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis
A Phase 2 study testing nitric oxide and oxygen in people with Sickle Cell Disease, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Randomized, double blind placebo controlled clinical trial to evaluate effectiveness and safety of inhaled nitric oxide for the treatment of sickle cell painful crisis in pediatric patients with sickle cell disease. Read more about this study
- Who is it for?
- Ages 9 to 22 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- nitric oxide and oxygen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to Aug 2013
- Phase
- Phase 2
- 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 9 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Hemoglobin SS, Hemoglobin Sß0thal or Hemoglobin SC documented by prior hemoglobin electrophoresis.
- Age 9 years or greater, age 22 years or less; pediatric age range, old enough to comply with mask and give reliable pain assessment score.
- Acute pain crisis defined as pain in abdomen, back and/or extremities that cannot be explained by a diagnosis other than sickle cell disease.
- Initial pain score at least 6 cm; to optimize the likelihood of observing a significant difference in change in pain score between INO treated and placebo groups. Based on data from our previous study, it is anticipated that patients will have an average pre-inhalation pain score of approximately 8 cm.
Who cannot join
- > 24 pain crises in the last 12 months. Patients with very frequent pain crisis may have biologic and/or psychosocial pathophysiology that differs from those with fewer pain crises.
- Pain crisis treated at a medical facility within the last 12 hours.
- Use of investigational drugs other than hydroxyurea within the last 30 days.
- Significant respiratory compromise (initial SaO2 < 90%) and/or patients likely to have acute chest syndrome (chest pain and infiltrate) will be eliminated.
- Clinically significant acute or chronic cardiac dysfunction.
- Acute priapism.
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- New focal neurologic symptoms.
- Concurrent documented or suspected bacterial or parvovirus infection.
- Temperature > 38.4ºC. These patients may have concomitant infection.
- Transfusion within 30 days or chronic transfusion therapy.
- Pregnant female
- Cigarette smoker > 1/2 ppd.
- Allergy to morphine
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02115
About this study
Randomized, double blind placebo controlled clinical trial to evaluate effectiveness and safety of inhaled nitric oxide for the treatment of sickle cell painful crisis in pediatric patients with sickle cell disease.
Read the detailed description
The specific aim of this study is to evaluate the clinical effectiveness of inhaled nitric oxide (INO) for the treatment of acute vaso-occlusive pain crisis in pediatric patients with sickle cell disease. Nitric oxide (NO) deficiency is known to be central to the pathophysiology of vaso-occlusion. The aim is unchanged from the original application. The study is a randomized, double blind, placebo controlled, clinical trial with eligible patients randomized to receive either NO (with 21% O2 final concentration) for 16 hrs with 8 hr wean (80 ppm 0-8 hrs, 40 ppm 9-16 hrs, 20 ppm 17-20 hrs, 10 ppm 21-24 hrs) or placebo (21% O2 alone) for 24 hrs. The null hypothesis is that there is no difference in change in mean pain score after 16 hours between patients treated with NO and placebo. The primary outcome measure of the study remains the difference in mean change in pain scores between groups as assessed using a 10 cm visual analogue pain scale (VAS). Secondary outcome measures also remain the same. The study is a next step to our completed FDA Orphan Product Development Grant funded study (FD-R-001686) that evaluated safety and efficacy of NO used for 4 hrs for treatment of vaso-occlusive crisis in pediatric patients with sickle cell disease.
- Conditions
- Sickle Cell Disease
- Being tested
- nitric oxide, oxygen
- Keywords
- sickle cell disease, pain crisis, vaso-occlusive crisis, nitric oxide
- 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
80 ppm 8 hrs, 40 ppm 8 hrs, 20 ppm 4 hrs, 10 ppm 4 hrs
oxygenDrug
oxygen fi02 21% (room air)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | inhaled NO Receives: Drug: nitric oxide |
| 2 | Placebo comparator | room air inhalation Receives: Drug: oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in change in mean pain score (visual analog scale) after 16 hours of treatment between patients treated with INO and placebo.
Measured: every 4 hrs x duration of hospitalization
Secondary outcomes (12)
Secondary outcome measures to evaluate efficacy
Measured: Duration of hospitalization, followup
Longitudinal analyses of change in VAS pain score over 16 hours.
Measured: every 4 hrs, duration of hospitalization
Change in pain score using a 5 point descriptive scale and a 5 point relief scale.
Measured: every 4 hours duration of hospitalization
Time to pain score less than 5 cm for 2 consecutive VAS pain assessments 4 hours apart and not using parenteral narcotics.
Measured: every 4 hrs, duration of hospitalization
Use of pain medication: cumulative dose of parenteral narcotic pain medications.
Measured: While patient on parenteral narcotic
Duration of hospitalization.
Measured: Time of discharge
Inflammatory markers/mediators.
Measured: 0, 16 and q 24 hrs during hospitalization
Secondary outcome measures to evaluate safety are:
Measured: 4, 8, 16, 24 hrs methb, constant NO2, 02 during inhalation
Maximum concentration of methemoglobin.
Measured: 0, 4, 8, 16, 24 hrs
Maximum concentration of nitrogen dioxide (NO2) delivered.
Measured: continuous over 24 hrs of inhalaiton
Minimum percent oxygen saturation of hemoglobin (by pulse oximetry).
Measured: continuous over 24 hrs of inhalation then every 4 hrs for duration of hospitalization
Maximum and minimum vital signs: pulse, respiratory rate, blood pressure.
Measured: every 4 hrs during hospitalization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2005 (estimated)
- Study startApr 2005
- Primary completionAug 2013
- Study completionAug 2013
Why it stopped: 18 or 20 enrolled, stopped due to paucity of available participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- FDA Office of Orphan Products Development
- Responsible party
- Principal investigator, Debra Weiner, Boston Children's Hospital
- Investigators
- Debra Weiner, MD, PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00142051
- Sponsor's protocol ID
- 04-09-119
- Other IDs
- FD-R-002560-01
- Status last verified
- Feb 2023
- First submitted
- 31 Aug 2005
- Last updated
- 23 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gladwin 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 21364138Weiner DL, Hibberd PL, Betit P, Cooper AB, Botelho CA, Brugnara C. Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease. JAMA. 2003 Mar 5;289(9):1136-42. doi: 10.1001/jama.289.9.1136.
PubMed 12622584
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitric Oxide for Pediatric Painful Sickle Crisis
- ClinicalTrials.gov ID
- NCT00142051
- Acronym / sponsor ID
- 04-09-119
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, pain crisis, vaso-occlusive crisis, nitric oxide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 18 or 20 enrolled, stopped due to paucity of available participants
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- FDA Office of Orphan Products Development
- Study start
- Apr 2005
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 2 Sep 2005 (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.
Randomized, double blind placebo controlled clinical trial to evaluate effectiveness and safety of inhaled nitric oxide for the treatment of sickle cell painful crisis in pediatric patients with sickle cell disease.
Detailed description
The specific aim of this study is to evaluate the clinical effectiveness of inhaled nitric oxide (INO) for the treatment of acute vaso-occlusive pain crisis in pediatric patients with sickle cell disease. Nitric oxide (NO) deficiency is known to be central to the pathophysiology of vaso-occlusion. The aim is unchanged from the original application. The study is a randomized, double blind, placebo controlled, clinical trial with eligible patients randomized to receive either NO (with 21% O2 final concentration) for 16 hrs with 8 hr wean (80 ppm 0-8 hrs, 40 ppm 9-16 hrs, 20 ppm 17-20 hrs, 10 ppm 21-24 hrs) or placebo (21% O2 alone) for 24 hrs. The null hypothesis is that there is no difference in change in mean pain score after 16 hours between patients treated with NO and placebo. The primary outcome measure of the study remains the difference in mean change in pain scores between groups as assessed using a 10 cm visual analogue pain scale (VAS). Secondary outcome measures also remain the same. The study is a next step to our completed FDA Orphan Product Development Grant funded study (FD-R-001686) that evaluated safety and efficacy of NO used for 4 hrs for treatment of vaso-occlusive crisis in pediatric patients with sickle cell disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: nitric oxideinhaled NO |
| 2 | Placebo comparator | Drug: oxygenroom air inhalation |
Who may qualify
- Ages
- 9 to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Hemoglobin SS, Hemoglobin Sß0thal or Hemoglobin SC documented by prior hemoglobin electrophoresis.
- Age 9 years or greater, age 22 years or less; pediatric age range, old enough to comply with mask and give reliable pain assessment score.
- Acute pain crisis defined as pain in abdomen, back and/or extremities that cannot be explained by a diagnosis other than sickle cell disease.
- Initial pain score at least 6 cm; to optimize the likelihood of observing a significant difference in change in pain score between INO treated and placebo groups. Based on data from our previous study, it is anticipated that patients will have an average pre-inhalation pain score of approximately 8 cm.
Key exclusion criteria (14 listed)
- > 24 pain crises in the last 12 months. Patients with very frequent pain crisis may have biologic and/or psychosocial pathophysiology that differs from those with fewer pain crises.
- Pain crisis treated at a medical facility within the last 12 hours.
- Use of investigational drugs other than hydroxyurea within the last 30 days.
- Significant respiratory compromise (initial SaO2 < 90%) and/or patients likely to have acute chest syndrome (chest pain and infiltrate) will be eliminated.
- Clinically significant acute or chronic cardiac dysfunction.
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 oxide80 ppm 8 hrs, 40 ppm 8 hrs, 20 ppm 4 hrs, 10 ppm 4 hrs | Drug | 1 |
| oxygenoxygen fi02 21% (room air) | Drug | 2 |
Primary outcome
Difference in change in mean pain score (visual analog scale) after 16 hours of treatment between patients treated with INO and placebo.
Time frame: every 4 hrs x duration of hospitalization
12 secondary outcomes
Secondary outcome measures to evaluate efficacy
Time frame: Duration of hospitalization, followup
Longitudinal analyses of change in VAS pain score over 16 hours.
Time frame: every 4 hrs, duration of hospitalization
Change in pain score using a 5 point descriptive scale and a 5 point relief scale.
Time frame: every 4 hours duration of hospitalization
Time to pain score less than 5 cm for 2 consecutive VAS pain assessments 4 hours apart and not using parenteral narcotics.
Time frame: every 4 hrs, duration of hospitalization
Use of pain medication: cumulative dose of parenteral narcotic pain medications.
Time frame: While patient on parenteral narcotic
Duration of hospitalization.
Time frame: Time of discharge
Inflammatory markers/mediators.
Time frame: 0, 16 and q 24 hrs during hospitalization
Secondary outcome measures to evaluate safety are:
Time frame: 4, 8, 16, 24 hrs methb, constant NO2, 02 during inhalation
Maximum concentration of methemoglobin.
Time frame: 0, 4, 8, 16, 24 hrs
Maximum concentration of nitrogen dioxide (NO2) delivered.
Time frame: continuous over 24 hrs of inhalaiton
Minimum percent oxygen saturation of hemoglobin (by pulse oximetry).
Time frame: continuous over 24 hrs of inhalation then every 4 hrs for duration of hospitalization
Maximum and minimum vital signs: pulse, respiratory rate, blood pressure.
Time frame: every 4 hrs during hospitalization
Results and safety
The study was stopped early (reason given: 18 or 20 enrolled, stopped due to paucity of available participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2023.
- Background: 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.
- Background: PubMed 12622584Weiner DL, Hibberd PL, Betit P, Cooper AB, Botelho CA, Brugnara C. Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease. JAMA. 2003 Mar 5;289(9):1136-42. doi: 10.1001/jama.289.9.1136.
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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.
Debra Weiner, MD, PhD principal investigator
Boston Children's Hospital
1 site 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 and oxygen in people with Sickle Cell Disease, run by Boston Children's Hospital at 1 site 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 4 inclusion and 14 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: stopped early, as of the sponsor's last update on 23 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study was stopped early (reason given: 18 or 20 enrolled, stopped due to paucity of available participants). Results are not available in the source record.
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?
Difference in change in mean pain score (visual analog scale) after 16 hours of treatment between patients treated with INO and placebo. (time frame: every 4 hrs x duration of hospitalization). 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 NCT00142051, 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 23 Feb 2023.