Trial reportJCI insight2018
A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS.
Trial report in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 63 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Trial of Inhaled Carbon Monoxide for the Treatment of Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)
A Phase II Trial of Inhaled Carbon Monoxide for the Treatment of Acute Respiratory Distress Syndrome (ARDS)
A Phase Ib Trial of Inhaled Carbon Monoxide for the Treatment of Pneumonia and Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)
Who cites it
63 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Biomarkers of mitochondrial dysfunction in acute respiratory distress syndrome: A systematic review and meta-analysis.Frontiers in medicine · 2022Pooled it
- Impact of differences in acute respiratory distress syndrome randomised controlled trial inclusion and exclusion criteria: systematic review and meta-analysis.British journal of anaesthesia · 2021Pooled it
- Between-trial heterogeneity in ARDS research.Intensive care medicine · 2021Pooled it
- Unraveling the potential of gasotransmitters as neurogenic and neuroprotective molecules: focus on Alzheimer's and Parkinson's diseases.Redox report : communications in free radical research · 2026Review
- Relevant insights from personalized inhaled carbon monoxide dosing in a safety study in pneumonia and ARDS.Respiratory research · 2026Article
- When Red Blood Cells Meet Carbon Monoxide: Yin and Yang in Medicines and Pharmaceuticals.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Carbon Monoxide Therapy: Evidence and Prospects for Preventing and Treating Retinal Diseases.Biomolecules · 2026Review
- Targeting the Gut in Sepsis: Therapeutic Potential of Medical Gases.Biomolecules · 2026Review
- Mitochondrial dysfunction in ARDS: unraveling the regulatory networks and therapeutic opportunities.Frontiers in immunology · 2026Review
- The mechanisms by which free heme exacerbates sepsis and the potential therapeutic targets.Frontiers in immunology · 2026Review
- Controlled Delivery of Gasotransmitters for Cardiovascular Therapy: Molecular Mechanisms, Engineered Platforms, and Translational Perspectives.International journal of nanomedicine · 2026Review
- CORM-A1 delivers carbon monoxide to the kidney and alleviates post-ischemic renal dysfunction in rat and swine models.Physiological reports · 2025Article
- Carbon Monoxide as a Molecular Modulator of Ischemia-Reperfusion Injury: New Insights for Translational Application in Organ Transplantation.International journal of molecular sciences · 2025Review
- Attenuation of mitochondrial dysfunction in a ventricular fibrillation swine model of cardiac arrest treated with carbon monoxide.Resuscitation · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide.Medicinal research reviews · 2025Review
- Therapeutic strategies to ameliorate mitochondrial oxidative stress in ischaemia-reperfusion injury: A narrative review.Clinical science (London, England : 1979) · 2025Review
- Proresolving Lipid Mediators in the Respiratory System.Annual review of physiology · 2025Review
- Composite Hyaluronic Acid Gas-Entrapping Materials to Promote Wound Healing.Biomacromolecules · 2025Article
- Metabolic Regulation in Acute Respiratory Distress Syndrome: Implications for Inflammation and Oxidative Stress.International journal of chronic obstructive pulmonary disease · 2025Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors.
Funding
Abstract
backgroundAcute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS.
methodsWe conducted a phase I dose escalation trial to assess feasibility and safety of low-dose iCO administration in patients with sepsis-induced ARDS. Twelve participants were randomized to iCO or placebo air 2:1 in two cohorts. Four subjects each were administered iCO (100 ppm in cohort 1 or 200 ppm in cohort 2) or placebo for 90 minutes for up to 5 consecutive days. Primary outcomes included the incidence of carboxyhemoglobin (COHb) level ≥10%, prespecified administration-associated adverse events (AEs), and severe adverse events (SAEs). Secondary endpoints included the accuracy of the Coburn-Forster-Kane (CFK) equation to predict COHb levels, biomarker levels, and clinical outcomes.
resultsNo participants exceeded a COHb level of 10%, and there were no administration-associated AEs or study-related SAEs. CO-treated participants had a significant increase in COHb (3.48% ± 0.7% [cohort 1]; 4.9% ± 0.28% [cohort 2]) compared with placebo-treated subjects (1.97% ± 0.39%). The CFK equation was highly accurate at predicting COHb levels, particularly in cohort 2 (R2 = 0.9205; P < 0.0001). Circulating mitochondrial DNA levels were reduced in iCO-treated participants compared with placebo-treated subjects.
conclusionPrecise administration of low-dose iCO is feasible, well-tolerated, and appears to be safe in patients with sepsis-induced ARDS. Excellent agreement between predicted and observed COHb should ensure that COHb levels remain in the target range during future efficacy trials.
trial registrationClinicalTrials.gov NCT02425579.
fundingNIH grants P01HL108801, KL2TR002385, K08HL130557, and K08GM102695.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.