Covid-19 living Data

Inhaled Nitric Oxide vs Standard care (RCT)

Hospitalized patients

FOREST PLOTS -2021-05-28

Studies description

Trial ISRCTN16806663
Publication Moni M, IMD (2022) (published paper)
Dates: 2020-09-20 to 2020-12-12
Funding: Public/non profit (Collaborating centre, the Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham.)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Single center / India Follow-up duration (days): 28
Inclusion criteria	Consenting adults 18-60 years of age confirmed diagnosis of SARS CoV-2 infection (using one or more of the following tests: antigen testing, Polymerase Chain Reaction, or the GeneXPert molecular platform AND moderate to severe respiratory symptoms, deemed to be secondary to Covid 19 (room air saturation on pulse oximetry 94% and a respiratory rate > 24 breaths/min).
Exclusion criteria	Mental obtundation and/or other contraindications to non-invasive ventilation (NIV) unwillingness to receive NIV were deemed candidates for invasive mechanical ventilation at the time of screening Kidney Disease Improving Global Outcomes (KDIGO) Stage II or higher renal failure a prevailing diagnosis of chronic renal failure known Glucose 6 Phosphate dehydrogenase deficiency or a baseline methemoglobin >3% hemoglobinopathies mean arterial pressure <65 mmHg presence of baseline pulmonary arterymhypertension (as adjudged by a tricuspid regurgitation velocity of >2.8 m/s on resting trans thoracic echocardiography) pregnant or lactating.
Interventions
	Treatment iNO administered in a crescendo-decrescendo fashion in doses from 10 ppm 0-5 mins to 80 ppm-0 ppm, 23-30 minutes, inhaled through a mask for 3 days
	Control Standard care
Participants
	Randomized participants : iNO=14 Standard care=15
	Characteristics of participants N= 29 Mean age : NR 18 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=25 Critical: n=0
Primary outcome
	In the register Viral load as defined by cycle threshold measured using Real-Time Polymerase Chain Reaction Surrogate CT ratio from nasopharyngeal swab collected at baseline 3, 5, 7, 10, and 14 days
	In the report Decline in viral load, as defined by a surrogate change in the RT-PCR cycle threshold; time to improvement of >2 points on the WHO Ordinal Scale (WOS)
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	High
General comment	In addition to the pre-print article, the retrospective trial registry was used in data extraction and risk of bias assessment. Neither the protocol nor statistical analysis plan was available. Inclusion criteria differ slightly between the pre-print article and the retrospective registry. The pre-print article included a co-primary outcome not included in the registry (improvement of > 2 points on a 8 point ordinal scale). The trial achieved it target sample size. The trial was assessed to be at a high risk of bias because of uneven withdrawal of consent in an open-label study (26.7% in the standard care arm versus none in the treatment arm) and because of some concerns in all other domains. This trial was updated on April 13th, 2022 after publication of study report.