Covid-19 Living Data

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 Inhaled Nitric Oxide 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 ( / ) Definition of Standard care: Oral Sildenafil at doses of 10 mg, thrice daily (to primarily prevent iNO rebound), for 5 days from trial enrolment; Additional therapies such as steroids (Dexamethasone), antivirals (remdesivir and favipiravir), antibiotics, fluid restriction, non-invasive ventilation (and/or transition to invasive ventilation) and anticoagulation were also considered and prescribed on an as needed basis by the immediate care team. All enrolled patients received care in a designated intensive care unit (ICU), where standard variables such as electrocardiography, non-invasive and/or invasive blood pressure and pulse oximetry, were continuously measured and recorded in a nursing chart. Additional monitoring was instituted according to the discretion of the ICU physician: the attending intensivist and care physicians decided on adjunct therapies such as fluid, vasopressors, non-Covid 19 related medication (if any, including anti-bacterials) and prescribed laboratory testing as they deemed fit.
Participants
	Randomized 29 participants (n₁=14 / n₂= 15)
	Characteristics of participants N=29 Mean age : 60.1 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 available	Protocol NR Statistical plan NR Data-sharing stated NR
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.