Covid-19 living Data

Combined metabolic cofactor supplementation vs Placebo (RCT)

Mild outpatients

FOREST PLOTS -2021-07-08

Studies description

Trial NCT04573153
Publication Altay O, Adv. Sci. (2021) (published paper)
Dates: 2020-07-15 to 2020-09-18
Funding: Mixed (ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation; The Plasma Profiling Facility team at SciLifeLab; Metabolon Inc.; ChromaDex (nicotinamide riboside provision); European Union's Horizon 2020 research and innovation programme)
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 safely Patients considered as inappropriate for this study for any reason Active participation in another clinical study Uncontrolled 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 dialysis Significant cardiovascular co-morbidity (i.e. heart failure) Patients with phenylketonuria (contraindicated for NAC) Known allergy for substances used in the study Alcohol consumption over 192 grams for men and 128 grams for women per week Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination Receipt of any experimental treatment for COVID-19 within the 30 days prior to the time of the screening evaluation.
Interventions
	Treatment CMCS 3.73 g L-carnitine tartrate, 2.55 g N-acetylcysteine, 1 g nicotinamide riboside chloride, and 12.35 g serine orally twice a day for 2 weeks
	Control Placebo
Participants
	Randomized participants : CMCS=71 Placebo=22
	Characteristics of participants N= 93 Mean age : NR 37 males Severity : Mild: n= 93/ Asymptomatic: n=0
Primary outcome
	In the register The evaluation of clinical efficacy of the combination of metabolic cofactor supplementation and hydroxychloroquine [ Time Frame: 14 days ]
	In the report Time to recovery (ending of all symptoms)
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication:
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 publication/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 phase III trial is reported in the same publication but extracted separately. 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.” On 08th of July, 2021, this study was updated based on the published report.