Severe MalariaPhase 1/2NCT01255215
Inhaled Nitric Oxide for the Adjunctive Therapy of Severe Malaria: a Randomized Controlled Trial
A Phase 1/2 study testing Inhaled Nitric Oxide in people with Severe Malaria, run by University Health Network, Toronto at 1 site in Uganda.
Trial summary
Despite the use of highly effective anti-malarial medications, 10-30% of African children with severe malaria will die, underscoring the need for adjunctive therapies that can be applied in endemic areas. Read more about this study
- Who is it for?
- Ages 1 year to 10 years
- Conditions the study is for
- Severe Malaria
- What is being tested?
- Inhaled Nitric Oxide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 1 siteUganda
- Study dates
- Jul 2011to Jan 2014
- Phase
- Phase 1/2
- 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 1 year to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 1-10 years
- Positive malaria rapid diagnostic test in the presence of any of the features of severe malaria
- Willing and able to complete follow up schedules for the study - 14 day and 6 months after hospital discharge
Who cannot join
- Baseline methemoglobinemia
- Known renal, cardiac, or hepatic disease or other chronic illnesses like diabetes, epilepsy, cerebral palsy, clinical AIDS
- Severe malnutrition
- Severe malarial anemia without other signs of severe malaria
Trial locations and contacts
1 site in 1 country.
About this study
Despite the use of highly effective anti-malarial medications, 10-30% of African children with severe malaria will die, underscoring the need for adjunctive therapies that can be applied in endemic areas. A clinical trial of adjunctive inhaled nitric oxide (iNO) in severe malaria is warranted on the basis of firm proof of concept from animal studies and a human study using the NO donor L-arginine, together with evidence of safety from clinical experience and trials of iNO for other conditions. Our objective is to determine whether supplemental iNO (80 ppm) in addition to Ugandan Standard of Care treatment reduces levels of Angiopoietin-2 (Ang-2), a quantitative biomarker of malaria severity, in children with severe malaria compared to Standard of Care treatment alone. We will conduct a randomized placebo-controlled trial among children 1-10 years of age admitted to Jinja Hospital (Uganda) with severe malaria to test the efficacy of inhaled nitric oxide in severe malaria.
Read the detailed description
Severe malaria remains a major cause of global morbidity and mortality. While the use of artemisinin-based antimalarial therapy has improved outcomes in severe malaria, the mortality rate remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which the angiogenic factors angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) have recently been shown to function as key regulators. Nitric oxide (NO) is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide gas (iNO) is a US FDA-approved treatment for hypoxic respiratory failure in neonates. Based on compelling data on the efficacy of iNO in experimental cerebral malaria in animal models, coupled with the documented safety of iNO in clinical practice and trials for other diseases, we propose a randomized clinical trial of iNO for the adjunctive treatment of severe malaria in Ugandan children.
- Conditions
- Severe Malaria
- Being tested
- Inhaled Nitric Oxide
- Keywords
- malaria, children
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled Nitric OxideDrug
Also called NO, nitrogen monoxide
Form: Gas (inhalational) Dose: 80 ppm Dosing schedule: Continuous Treatment period: Maximum 72 hours (may be discontinued earlier if patient recovers and no longer tolerates face mask)
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Nitric Oxide | Experimental | iNO, a gaseous molecule, will be administered by inhalational route over a maximum period of 72 hours. Receives: Drug: Inhaled Nitric Oxide |
| Room air | Placebo comparator | Room air will be delivered by air compressor through an indistinguishable mask system. Receives: Drug: Inhaled Nitric Oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in serum angiopoietin-2 level
Daily Ang-2 measurements over the first 72 hours of hospital admission will be the primary efficacy outcome. Elevated Ang-2 levels are associated with poor clinical outcome in severe malaria and Ang-2 has been used to follow disease progression and recovery in previous studies of malaria. Thus, Ang-2 is an objective, quantitative surrogate marker of disease severity, validated for longitudinal follow-up of patients with malaria.
Measured: Admission through 72 hours
Secondary outcomes (4)
Mortality
Measured: 48 hours and 14 days after admission
Time to hospital discharge
Recovery times (time to fever resolution, time to sit unsupported, and time to hospital discharge) are standard, clinically relevant outcomes in other therapeutic trials for malaria.
Measured: From admission to approximately 72 hours
Time to parasite clearance.
Parasitological efficacy outcome; quantitative assessment of parasite density by light microscopy of Giemsa-stained thin smears.
Measured: From admission to approximately 72 hours
Biomarkers and genetic determinants of endothelial activation, inflammation and coagulopathy, to be determined.
Biomarkers and genetic determinants of severe malaria pathogenesis may provide additional insight into the pathways and processes altered in cerebral malaria and affected by iNO delivery. We plan to examine biomarkers of endothelial activation, inflammation including cytokines, and coagulopathy which are central to the pathophysiology of severe malaria. In addition, genetic pathways involved in severe malaria and response to iNO will be investigated.
Measured: From admission to approximately 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2010 (estimated)
- Study startJul 2011
- Primary completionJul 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Severe MalariaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Makerere University, University of Toronto
- Responsible party
- Sponsor
- Investigators
- Michael Hawkes, MD, Study director, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01255215
- Sponsor's protocol ID
- iNO RCT
- Status last verified
- Dec 2012
- First submitted
- 5 Dec 2010
- Last updated
- 20 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med. 1997 Feb 27;336(9):597-604. doi: 10.1056/NEJM199702273360901.
PubMed 9036320Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, Rhines J, Chang CT. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group. Pediatrics. 1998 Mar;101(3 Pt 1):325-34. doi: 10.1542/peds.101.3.325.
PubMed 9480993Dobyns EL, Cornfield DN, Anas NG, Fortenberry JD, Tasker RC, Lynch A, Liu P, Eells PL, Griebel J, Baier M, Kinsella JP, Abman SH. Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure. J Pediatr. 1999 Apr;134(4):406-12. doi: 10.1016/s0022-3476(99)70196-4.
PubMed 10190913Michael JR, Barton RG, Saffle JR, Mone M, Markewitz BA, Hillier K, Elstad MR, Campbell EJ, Troyer BE, Whatley RE, Liou TG, Samuelson WM, Carveth HJ, Hinson DM, Morris SE, Davis BL, Day RW. Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1372-80. doi: 10.1164/ajrccm.157.5.96-10089.
PubMed 9603111Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K Jr, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998 Jan;26(1):15-23. doi: 10.1097/00003246-199801000-00011.
PubMed 9428538Troncy E, Collet JP, Shapiro S, Guimond JG, Blair L, Ducruet T, Francoeur M, Charbonneau M, Blaise G. Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1483-8. doi: 10.1164/ajrccm.157.5.9707090.
PubMed 9603127Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Med. 1999 Sep;25(9):911-9. doi: 10.1007/s001340050982.
PubMed 10501745Gerlach H, Keh D, Semmerow A, Busch T, Lewandowski K, Pappert DM, Rossaint R, Falke KJ. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study. Am J Respir Crit Care Med. 2003 Apr 1;167(7):1008-15. doi: 10.1164/rccm.2108121.
PubMed 12663340Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis K Jr, Kelly KM, Smith TC, Small RJ; Inhaled Nitric Oxide in ARDS Study Group. Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. JAMA. 2004 Apr 7;291(13):1603-9. doi: 10.1001/jama.291.13.1603.
PubMed 15069048Conroy AL, Hawkes MT, Elphinstone R, Opoka RO, Namasopo S, Miller C, John CC, Kain KC. Chitinase-3-like 1 is a biomarker of acute kidney injury and mortality in paediatric severe malaria. Malar J. 2018 Feb 15;17(1):82. doi: 10.1186/s12936-018-2225-5.
PubMed 29448936Bangirana P, Conroy AL, Opoka RO, Hawkes MT, Hermann L, Miller C, Namasopo S, Liles WC, John CC, Kain KC. Inhaled nitric oxide and cognition in pediatric severe malaria: A randomized double-blind placebo controlled trial. PLoS One. 2018 Jan 25;13(1):e0191550. doi: 10.1371/journal.pone.0191550. eCollection 2018.
PubMed 29370261Conroy AL, Hawkes M, Hayford K, Hermann L, McDonald CR, Sharma S, Namasopo S, Opoka RO, John CC, Liles WC, Miller C, Kain KC. Methemoglobin and nitric oxide therapy in Ugandan children hospitalized for febrile illness: results from a prospective cohort study and randomized double-blind placebo-controlled trial. BMC Pediatr. 2016 Nov 4;16(1):177. doi: 10.1186/s12887-016-0719-2.
PubMed 27814710Hawkes MT, Conroy AL, Opoka RO, Hermann L, Thorpe KE, McDonald C, Kim H, Higgins S, Namasopo S, John C, Miller C, Liles WC, Kain KC. Inhaled nitric oxide as adjunctive therapy for severe malaria: a randomized controlled trial. Malar J. 2015 Oct 29;14:421. doi: 10.1186/s12936-015-0946-2.
PubMed 26510464Hawkes M, Opoka RO, Namasopo S, Miller C, Thorpe KE, Lavery JV, Conroy AL, Liles WC, John CC, Kain KC. Inhaled nitric oxide for the adjunctive therapy of severe malaria: protocol for a randomized controlled trial. Trials. 2011 Jul 13;12:176. doi: 10.1186/1745-6215-12-176.
PubMed 21752262Hawkes M, Opoka RO, Namasopo S, Miller C, Conroy AL, Serghides L, Kim H, Thampi N, Liles WC, John CC, Kain KC. Nitric oxide for the adjunctive treatment of severe malaria: hypothesis and rationale. Med Hypotheses. 2011 Sep;77(3):437-44. doi: 10.1016/j.mehy.2011.06.003. Epub 2011 Jul 13.
PubMed 21745716
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitric Oxide for the Adjunctive Therapy of Severe Malaria: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01255215
- Acronym / sponsor ID
- iNO RCT
- Conditions
- Severe Malaria
- Keywords
- malaria, children
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Makerere University, University of Toronto
- Study start
- Jul 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 7 Dec 2010 (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.
Despite the use of highly effective anti-malarial medications, 10-30% of African children with severe malaria will die, underscoring the need for adjunctive therapies that can be applied in endemic areas. A clinical trial of adjunctive inhaled nitric oxide (iNO) in severe malaria is warranted on the basis of firm proof of concept from animal studies and a human study using the NO donor L-arginine, together with evidence of safety from clinical experience and trials of iNO for other conditions. Our objective is to determine whether supplemental iNO (80 ppm) in addition to Ugandan Standard of Care treatment reduces levels of Angiopoietin-2 (Ang-2), a quantitative biomarker of malaria severity, in children with severe malaria compared to Standard of Care treatment alone. We will conduct a randomized placebo-controlled trial among children 1-10 years of age admitted to Jinja Hospital (Uganda) with severe malaria to test the efficacy of inhaled nitric oxide in severe malaria.
Detailed description
Severe malaria remains a major cause of global morbidity and mortality. While the use of artemisinin-based antimalarial therapy has improved outcomes in severe malaria, the mortality rate remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which the angiogenic factors angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) have recently been shown to function as key regulators. Nitric oxide (NO) is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide gas (iNO) is a US FDA-approved treatment for hypoxic respiratory failure in neonates. Based on compelling data on the efficacy of iNO in experimental cerebral malaria in animal models, coupled with the documented safety of iNO in clinical practice and trials for other diseases, we propose a randomized clinical trial of iNO for the adjunctive treatment of severe malaria in Ugandan children.
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 |
|---|---|---|
| Inhaled Nitric Oxide | Experimental | Drug: Inhaled Nitric OxideiNO, a gaseous molecule, will be administered by inhalational route over a maximum period of 72 hours. |
| Room air | Placebo comparator | Drug: Inhaled Nitric OxideRoom air will be delivered by air compressor through an indistinguishable mask system. |
Who may qualify
- Ages
- 1 year to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Age 1-10 years
- Positive malaria rapid diagnostic test in the presence of any of the features of severe malaria
- Willing and able to complete follow up schedules for the study - 14 day and 6 months after hospital discharge
Key exclusion criteria (4 listed)
- Baseline methemoglobinemia
- Known renal, cardiac, or hepatic disease or other chronic illnesses like diabetes, epilepsy, cerebral palsy, clinical AIDS
- Severe malnutrition
- Severe malarial anemia without other signs of severe malaria
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 |
|---|---|---|
| Inhaled Nitric OxideAlso: NO, nitrogen monoxideForm: Gas (inhalational) Dose: 80 ppm Dosing schedule: Continuous Treatment period: Maximum 72 hours (may be discontinued earlier if patient recovers and no longer tolerates face mask) | Drug | Inhaled Nitric Oxide, Room air |
Primary outcome
Change in serum angiopoietin-2 level
Time frame: Admission through 72 hours
Daily Ang-2 measurements over the first 72 hours of hospital admission will be the primary efficacy outcome. Elevated Ang-2 levels are associated with poor clinical outcome in severe malaria and Ang-2 has been used to follow disease progression and recovery in previous studies of malaria. Thus, Ang-2 is an objective, quantitative surrogate marker of disease severity, validated for longitudinal follow-up of patients with malaria.
4 secondary outcomes
Mortality
Time frame: 48 hours and 14 days after admission
Time to hospital discharge
Time frame: From admission to approximately 72 hours
Time to parasite clearance.
Time frame: From admission to approximately 72 hours
Biomarkers and genetic determinants of endothelial activation, inflammation and coagulopathy, to be determined.
Time frame: From admission to approximately 72 hours
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 20 Feb 2014.
- Results publication: PubMed 9036320Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med. 1997 Feb 27;336(9):597-604. doi: 10.1056/NEJM199702273360901.
- Results publication: PubMed 9480993Davidson D, Barefield ES, Kattwinkel J, Dudell G, Damask M, Straube R, Rhines J, Chang CT. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicenter study. The I-NO/PPHN Study Group. Pediatrics. 1998 Mar;101(3 Pt 1):325-34. doi: 10.1542/peds.101.3.325.
- Results publication: PubMed 10190913Dobyns EL, Cornfield DN, Anas NG, Fortenberry JD, Tasker RC, Lynch A, Liu P, Eells PL, Griebel J, Baier M, Kinsella JP, Abman SH. Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure. J Pediatr. 1999 Apr;134(4):406-12. doi: 10.1016/s0022-3476(99)70196-4.
- Results publication: PubMed 9603111Michael JR, Barton RG, Saffle JR, Mone M, Markewitz BA, Hillier K, Elstad MR, Campbell EJ, Troyer BE, Whatley RE, Liou TG, Samuelson WM, Carveth HJ, Hinson DM, Morris SE, Davis BL, Day RW. Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1372-80. doi: 10.1164/ajrccm.157.5.96-10089.
- Results publication: PubMed 9428538Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K Jr, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998 Jan;26(1):15-23. doi: 10.1097/00003246-199801000-00011.
- Results publication: PubMed 9603127Troncy E, Collet JP, Shapiro S, Guimond JG, Blair L, Ducruet T, Francoeur M, Charbonneau M, Blaise G. Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1483-8. doi: 10.1164/ajrccm.157.5.9707090.
- Results publication: PubMed 10501745Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Med. 1999 Sep;25(9):911-9. doi: 10.1007/s001340050982.
- Results publication: PubMed 12663340Gerlach H, Keh D, Semmerow A, Busch T, Lewandowski K, Pappert DM, Rossaint R, Falke KJ. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study. Am J Respir Crit Care Med. 2003 Apr 1;167(7):1008-15. doi: 10.1164/rccm.2108121.
- Results publication: PubMed 15069048Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis K Jr, Kelly KM, Smith TC, Small RJ; Inhaled Nitric Oxide in ARDS Study Group. Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. JAMA. 2004 Apr 7;291(13):1603-9. doi: 10.1001/jama.291.13.1603.
- Derived from this study: PubMed 29448936Conroy AL, Hawkes MT, Elphinstone R, Opoka RO, Namasopo S, Miller C, John CC, Kain KC. Chitinase-3-like 1 is a biomarker of acute kidney injury and mortality in paediatric severe malaria. Malar J. 2018 Feb 15;17(1):82. doi: 10.1186/s12936-018-2225-5.
- Derived from this study: PubMed 29370261Bangirana P, Conroy AL, Opoka RO, Hawkes MT, Hermann L, Miller C, Namasopo S, Liles WC, John CC, Kain KC. Inhaled nitric oxide and cognition in pediatric severe malaria: A randomized double-blind placebo controlled trial. PLoS One. 2018 Jan 25;13(1):e0191550. doi: 10.1371/journal.pone.0191550. eCollection 2018.
- Derived from this study: PubMed 27814710Conroy AL, Hawkes M, Hayford K, Hermann L, McDonald CR, Sharma S, Namasopo S, Opoka RO, John CC, Liles WC, Miller C, Kain KC. Methemoglobin and nitric oxide therapy in Ugandan children hospitalized for febrile illness: results from a prospective cohort study and randomized double-blind placebo-controlled trial. BMC Pediatr. 2016 Nov 4;16(1):177. doi: 10.1186/s12887-016-0719-2.
Related trials for Severe Malaria
Active, not recruiting
IGHID 12334 - After the Flood: Optimal Strategies to Prevent Malaria Epidemics Caused by Severe Flooding
Malaria Infection, Malaria Falciparum
Recruiting
Platelet-Directed Whole Blood Transfusion Strategy for Malaria
Severe Malaria, Thrombocytopenia
RecruitingPhase 4
Post-discharge Malaria Chemoprevention Implementation Trial in Benin
Severe Malaria, Severe Anaemia
Active, not recruitingPhase 3
Monoclonal Antibodies in Children With Severe Anaemia or Severe Malaria to Prevent Malaria After Hospital Discharge
Malaria, Severe Malaria
Enrolling by invitationObservational study
Severe Malaria in Remote Areas- Closing the Evidence Gap
Severe Malaria
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.
Michael Hawkes, MD study director
University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Inhaled Nitric Oxide in people with Severe Malaria, run by University Health Network, Toronto at 1 site in Uganda.
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 3 inclusion and 4 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 20 Feb 2014. 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 Uganda. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 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?
Change in serum angiopoietin-2 level (time frame: Admission through 72 hours). 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 NCT01255215, which also lists 15 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 20 Feb 2014.