Covid-19 Living Data

Trial NCT04573153
Publication Altay O, medRxiv, 2020 (preprint)
Dates: 2020-07-15 to 2020-09-18
Funding: Private (This work was supported by Knut and Alice Wallenberg Foundation. ChromaDex (Irvine, CA, USA) for providing NR (nicotinamide riboside).)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Single center / Turkey Follow-up duration (days): 14
Inclusion criteria	Patients of both genders over 18 years of age Written informed consent obtained from the subjects prior to any procedures related to the study Understand all procedures to be applied within the scope of the study protocol Ambulatory patients with symptoms diagnosed with COVID-19 with real time PCR test result positivity in the last 72 hours Patients with stable clinical course and who could be treated on an ambulatory basis
Exclusion criteria	Patients who has partial oxygen saturation below 90% or with severe clinical status requiring admission to critical care unit Inability or unwillingness to give written informed consent Physician makes a decision that trial involvement is not in patients' best interest, or any condition that does not allow the protocol to be followed safelyPatients considered as inappropriate for this study for any reasonActive participation in another clinical studyUncontrolled Type 1 or type 2 diabetes Severe liver disease (e.g. Child Pugh score ≥ C, AST>5 times upper limit)Patients with known severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysisSignificant cardiovascular co-morbidity (i.e. heart failure)Patients with phenylketonuria (contraindicated for NAC)Known allergy for substances used in the studyAlcohol consumption over 192 grams for men and 128 grams for women per weekPregnant or breastfeeding, or positive pregnancy test in a pre-dose examinationReceipt of any experimental treatment for COVID-19 within the 30 days prior to the time of the screening evaluation.
Interventions
	Treatment Combined metabolic cofactor supplementation (39.26 g/day (L-Carnitine tartrate, 7.46 g/day ) Co-Intervention: Standard care Duration : 14 days
	Control Placebo (lactose 60 mL) Duration : 14 days
Participants
	Randomized 93 participants (n₁=71 / n₂= 22)
	Characteristics of participants N=93 Mean age : NR 37 males Severity : Mild: n=93 / Moderate: n=0/ Severe: n=0 Critical: n=0
Primary outcome
	In the register No
	In the report The primary outcome was the time to recovery (ending of all symptoms)
Documents avalaible	Protocol NR Statistical plan NR Data-sharing stated Yes
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	Some concerns
General comment	In addition to the pre-print study report, the study registration and supplementary materials were used in data extraction and assessment of risk of bias. Neither study protocol nor statistical analysis plan was available. Completed single-center phase II study with 100 patients; the research will continue as a multi-center Phase III study with a further 300 patients. There were some changes in the primary outcome between the trial registration and the reported study, but the authors are transparent about this and report that all protocol amendments were authorized and approved by the sponsor, the institutional review board or independent ethics committee, and the pertinent regulatory authorities. The authors' descriptions of blinding in the study are unclear. The study is described as open-label in the report and registration, and in the limitations authors report “the trial was not blinded”. But they also report that the trial is placebo-controlled and that “Except the investigator, all other clinical staff involved in the daily surveying of the study participants blinded to whether the patients were receiving placebo or active. The patients were also unaware if they were receiving active or placebo.”