Table 2.
Ongoing randomized controlled trials on nitric oxide for the treatment of various clinical conditions.
| Trial | Aim/hypothesis | Population (N) | Treatment group | Control group | NO dose | Primary endpoint |
|---|---|---|---|---|---|---|
|
| ||||||
| Respiratory failure NCT04776408 | Measure dead space or shunt fraction before and after iNO | Adults (100) | Lung recruitment maneuver + iNO | Lung recruitment maneuver | n.a. | V/Q mismatch through EIT |
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| Covid19 | ||||||
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| NO-COVID-19 NCT04388683 | iNO ↓ progression to advanced disease | Adults (42) | iNO | Conventional care | 20 ppm | Progression to ↑ FiO2, ventilatory support or death |
| NCT05012319 | NO ↓ need of urgent care | Adults (500) | NO nasal spray | Placebo | n.a. | Need of urgent care |
| NCT04397692 | Safety | Adults (20) | iNO | Conventional care | 80 ppm | Time to deterioration |
| Lei, 2020 [71] | iNO ↑ oxygenation | Adults (200) | iNO 80 ppm for 2 d, then 40 ppm, then weaning | Conventional care | 40 ppm | Change in P/F at 2 d |
| Lei, 2020 [72] | iNO prevents progression of mild/moderate Covid19 | Adults (70) | iNO for 20–30 min bid for 14 d + conventional care | Conventional care | 140–180 ppm | Need for intubation and MV |
| NCT04601077 | Safety | Adults (100) | NO lozenges | Placebo | 30 mg | Low BP and dizziness incidence |
| NCT04383002 | iNO safety, antiviral effect and prevention of progression to HRF | Adults (20) | iNO for 6 h/d for 2 days + standard of care | Standard of care | 160 ppm | Covid19 PCR status at 7 d |
| NO COV-ED NCT04338828 | iNO ↑ respiratory status, prevent hospitalization and t clinical course in ED | Adults (47) | iNO for 20–30 min | O2 2 l/min | 140–300 ppm | Rate of return to ED w/in 28 d |
| COViNOX NCT04421508 | Efficacy and safety of iNO | Adults (500) | Pulsed iNO | Pulsed placebo | 125mcg/kg IBW/h | Death or HRF at 28 d |
| NICOR NCT04476992 | Safety | Adults (20) | iNO high dose 30 min bid for 14 d | iNO high dose 30min bid + continuous iNO low dose for 14 d | High dose: 200 ppm | Change in MetHb level at 2 d |
| Low dose: 20 ppm | ||||||
| NCT04443868 | Efficacy of NO to ↓ infection duration | Adults (50) | NO nasal irrigation daily (240 ml) | Normal saline nasal irrigation (240 ml) | 14 ppm | Sars-Cov-2 viral load baseline through 6 d |
| NCT04460183 | Efficacy of RESP301 (NO generating solution) in ↓ progression of Covid19 and safety | Adults (300) | Inhaled RESP301 tid up to 10 d + conventional care | Conventional care | n.a. | Progression on the modified WHO ordinal scale by 14 d |
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| Pulmonary Arterial Hypertension | ||||||
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| NCT01457781 | Efficacy and safety | Adults (80) | Pulsed iNO up to 24h/ day for 16 w | Placebo | 0.025–0.075 mg/kg IBW/h | Change in PVR |
| NCT03267108 | Efficacy and safety | Adults (300) | Pulsed iNO | Placebo | 0.045 mg/kg IBW/h | Change in moderate to vigorous activity, adverse events |
| NCT03576885 | iNO ↓ death, PAH and BPD incidence | Newborns (138) | iNO for 14 d or resolution of PAH | Placebo | 20 ppm | Death, BPD incidence |
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| NO during CPB | ||||||
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| Marrazzo, 2019 [73] | NO ↓ AKI in pts w/endothelial dysfunction | Adults (250) | NO | Placebo | 80 ppm | AKI occurrence |
| NCT03946462 | NO ↓ AKI | Newborns (24) | NO | Placebo | 20 ppm | NGAL/Cystatin-C levels |
| NCT04216927 | NO ↓ AKI after CPB | Newborns (40) | NO | Placebo | 20 ppm | AKI incidence |
| Schlapbach, 2019 | NO ↓ MV duration |
Infants (1320) | NO | Placebo | 20 ppm | VFD at 28 d |
| NASO NCT03661385 | NO ↓ post-operative MAEs | Children, Adults (900) | NO | Standard care | 20 ppm | MAEs: cardiac arrest, emergency chest |
| NCT05101746 | NO is neuro and renal protective | Children (50) | NO | Standard care | 20 ppm | opening, ECMO, death GFAP and NGAL levels |
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| Brain Injury | ||||||
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| NCT03260569 | Effect of iNO on gas exchange in TBI | Adults (38) | iNO | Placebo | 20 ppm | Change in paO2 |
Legend:
decreases/decreased
increases/increased.
Abbreviations: AKI, acute kidney injury; bid, bis in die; BP, blood pressure; BPD, bronchopulmonary dysplasia; CPB, cardiopulmonary bypass; d, day(s), ECMO, extracorporeal membrane oxygenation; EIT, electrical impedance tomography; FiO2, fraction of inspired oxygen; GFAP, glial fibrillary acid protein; h, hour(s); HRF, hypoxic respiratory failure; IBW, ideal body weight; iNO, inhaled nitric oxide; MAE, major adverse event; MetHb, methemoglobin; min, minutes; MV, mechanical ventilation; n.a., not available; NGAL, neutrophil gelatinase-associated lipocalin; NO, nitric oxide; P/F, partial oxygen pressure-to-fraction of inspired oxygen ratio; PAH, pulmonary arterial hypertension; paO2, partial pressure of oxygen; PCR, polymerase chain reaction; ppm, part per million; PVR, pulmonary vascular resistances; tid, tris in die; VFD, ventilator-free days; w/with; w/in, within.