Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial.

BACKGROUND: No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. METHODS: Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (-1.41 vs -1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (-3.37 vs -3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. CONCLUSIONS: In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.

A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19.

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. METHODS: We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).

Soluble fibre (Plantago ovata husk) reduces plasma low-density lipoprotein (LDL) cholesterol, triglycerides, insulin, oxidised LDL and systolic blood pressure in hypercholesterolaemic patients: A randomised trial.

UNLABELLED: The objective was to evaluate whether the soluble fibre Plantago ovata (Po)-husk improves cardiovascular disease (CVD) risk biomarkers including low-density lipoprotein cholesterol (LDL-C). METHODS: In a multi-centred, double-blind, placebo-controlled, parallel, randomised trial conducted in primary care-clinics in Spain, France and Holland, mild-moderate hypercholesterolaemic patients (age range: 43-67 years) received 14 g/d of Po-husk (n=126) or placebo (microcrystalline-cellulose 14 g/d; n=128) in a low saturated fat diet for 8 weeks. Subsequently, if LDL-C remained > or = 3.35 mmol/L [130 mg/dL], participants proceeded with the fibre plus simvastatin (20mg/d) for further 8 weeks. Lipid profile, blood pressure (BP), insulin, oxidised LDL and some gene polymorphisms involved in CVD risk were measured. RESULTS: Relative to placebo, Po-husk reduced plasma LDL-C by -6% (P<0.0002), total cholesterol (TC) by -6%, triglycerides (TG) by -21.6%, apolipoprotein (Apo) B-100 by -6.7%, oxidised LDL by a mean of -6.82 U/L (95%CI: 3.15-10.48), insulin by -4.68 pmol/L (95%CI: 0.68-8.67) and systolic BP by -4.0mm Hg (95%CI; 1.2-6.7) (P<0.05). The TG-lowering effect in the Po-husk group was magnified by variants in plasminogen-activator-inhibitor (PAI-1; rs1799768) and fatty acid-binding protein (FABP-2; rs1799883) genes. At 16 weeks, the intra-group action of simvastatin (20mg/d) added to Po-husk or placebo was a similar LDL-C reduction. CONCLUSIONS: Po-husk, apart from lowering LDL-C, also reduced TG, TG related to certain gene variants, TC, Apo B-100, oxLDL, insulin-resistance and systolic BP in mild-moderate hypercholesterolaemic individuals. Thus, the target patients to receive Po-husk would be those who present a cluster of various CVD risk factors, such as metabolic syndrome.

Effect of two doses of a mixture of soluble fibres on body weight and metabolic variables in overweight or obese patients: a randomised trial.

The aim of the study was to compare the effect of the administration of a mixture of fibres on body weight-loss, satiety, lipid profile and glucose metabolism. We included 200 overweight or obese patients in a parallel, double-blind, placebo-controlled clinical trial, who were randomised to receive, in the context of an energy-restricted diet for a period of 16 weeks, a mixed fibre dose (3 g Plantago ovata husk and 1 g glucomannan) twice (b.i.d. group) or three times daily (t.i.d. group) or placebo. Weight change was the primary efficacy endpoint. Satiety, dietary compliance, lipid profile, glucose tolerance, insulin resistance and high-sensitivity C-reactive protein were secondary endpoints. Weight loss tended to be higher after both doses of fibre (-4.52 (SD 0.56) and -4.60 (SD 0.55) kg) than placebo (-0.79 (SD 0.58) kg); the differences in changes between groups were not statistically significant. Postprandial satiety increased in both fibre groups compared to the placebo. The differences between groups in LDL-cholesterol levels were significant (P = 0.03), with greater reductions in the two fibre-supplemented groups (-0.38 (SD 0.10) and -0.24 (SD 0.09) mmol/l in the b.i.d. and t.i.d. groups v. -0.06 (SD 0.09) mmol/l in placebo group). A similar pattern was observed for changes in total cholesterol:HDL-cholesterol and HDL-cholesterol:LDL-cholesterol ratios. Interventions were well tolerated and had no effects on HDL-cholesterol, glucose and insulin concentrations, glucose tolerance or high-sensitivity C-reactive protein. In conclusion, a 16-week dietary supplement of soluble fibre in overweight or obese patients was well tolerated, induced satiety and had beneficial effects on some CVD risk factors, the most important of which was a significant decrease in plasma LDL-cholesterol concentrations.

Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without diphtheria or tetanus vaccination for 20 years or with an unknown vaccination history. RESEARCH DESIGN AND METHODS: Double-blind, randomized, controlled clinical trial. Primary vaccination with either three doses of dTpa, one dose of dTpa-IPV followed by two doses of Td, or three doses of Td vaccine (control) administered in a 0-1-6-month schedule. MAIN OUTCOME MEASURES: Blood samples were collected before commencement and 1 month after each dose. Local and general symptoms were solicited for 15 days after each dose. RESULTS: A total of 460 adults were enrolled, of whom over 48% did not have protective antibody concentrations against diphtheria and tetanus. One month after dose 3 > 99% had seroprotective anti-diphtheria and tetanus antibodies. Three doses were required to maximize anti-diphtheria seroprotection rates. A vaccine response to pertussis antigens was observed in > 92% of dTpa and dTpa-IPV recipients after dose 1. One month after dTpa-IPV, > 98.4% had seroprotective anti-polio titres. No statistically significant differences in local or general symptoms between groups were observed. CONCLUSIONS: dTpa and dTpa-IPV can provide primary vaccination of adults. Combinations of dTpa or dTpa-IPV can be used to replace Td and provide booster vaccination against pertussis and polio simultaneously with diphtheria and tetanus, even in situations where the primary vaccination history is unknown.