Table 1 History of carbon monoxide inhalational clinical trials including healthy volunteers and patients. The lower part represents the studies, which have been withdrawn for various reasons. (This list is not exhaustive)
From: Carbon monoxide in intensive care medicine—time to start the therapeutic application?!
Ref. | Year | First author | Number of participants | Carbon monoxide dose | CO-Hb | Outcome/marker |
|---|---|---|---|---|---|---|
52 | 1973 | R.D. Steward | Not reported | 100 ppm for 8 h | 11–13% | Feasibility study |
53 | 1975 | J.E. Peterson | 22 volunteers | 50, 100, and 200 ppm for 5.25 h | 1–20% | Feasibility study, check of Coburn-Forster-Kane equation |
55 | 1997 | M. Hausberg | 10 volunteers | 30 min of 1000 ppm followed by 30 min of 100 ppm | 8.3 ± 0.5% | Acute sympathetic and hemodynamic effects, no differences between groups |
54 | 2001 | Ren | 11 subjects | 4000 ppm until CO-Hb = 10% | 9.7 ± 0.1 | Respiratory response to prolonged hypoxia, no differences between groups |
56 | 2001 | Zevin | 12 healthy smokers | 1200–1500 ppm and smoking of at least 20 cigarettes per day for 7 days | 5 ± 1% | No differences in blood pressure or respiratory rate; analysis of platelet factor 4 and urine epinephrine and norepinephrine |
58 | 2005 | Mayr | 9 volunteers | 500 ppm for 1 h after intravenous LPS injection (2 ng/kg BW) | 6.5–7.7% | TNF, IL-1, IL-6, IL-8 concentrations in plasma showed no differences |
62 | 2005 | Resch | 15 volunteers | 500 ppm for 1 hour | 8.5 ± 0.9% | Significant increase in retinal and choroidal blood flow |
59 | 2007 | Bathoorn | 20 COPD patients | 100–125 ppm CO for 2 h on 4 consecutive days | 4.5% | Trend in the reduction of sputum eosinophils, improvement in response to metacholine |
57 | 2009 | Rhodes | 6 subjects | 100 ppm for 1 h for 5 days | 3.3 ± 0.6% | Significant increase in SOD, HO-1, mitofusin, ATPase-6 and COX-1 proteins due to CO inhalation |
60 | 2015 | Pecorella | 19 subjects | 200 ppm for 1 h for 5 days | 5.4 ± 0.8% | Significant increase in muscle citrate synthase, mitochondrial density and GLUT4 |
61 | 2016 | Ryan | 18 volunteers | 1.2 mL/kg BW for 30 s for 10 days | 4.4 ± 0.4% | No changes in haemoglobin mass, aerobic performance or peak power exercise tolerance |
Studies withdrawn | ||||||
2007 | NCT00531856 | % | 5.97 mg/L of carbon monoxide in 30% oxygen post transplantation (3 different doses) | n.a. | Primary outcome: Evaluate the safety and tolerability, secondary: incidence of delayed graft dysfunction (study withdrawn) | |
2012 | NCT01523548 | % | 150 ppm for 3 h for 3 weeks | n.a. | Primary outcome: Evidence of a decrease in pulmonary vascular resistance post-therapy (Study withdrawn) | |
2010 | NCT01050712 | % | Depending on a healthy control group | n.a. | Primary outcome: incidence and duration of postoperative ileus (Study withdrawn) | |
2012 | NCT01727167 | % | 200 ppm for 1 h | n.a. | Primary outcome: Biochemical Markers for Mitochondrial Biogenesis in aortic valve surgery (Study withdrawn) |