Homeopathy for COVID-19 in primary care: A randomized, double-blind, placebo-controlled trial (COVID-Simile study).

BACKGROUND: Different homeopathic approaches have been used as supportive care for coronavirus disease 2019 (COVID-19) cases, but none has been tested in a clinical trial. OBJECTIVES: To investigate the effectiveness and safety of the homeopathic medicine, Natrum muriaticum LM2, for mild cases of COVID-19. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A randomized, double-blind, two-armed, parallel, single-center, placebo-controlled clinical trial was conducted from June 2020 to April 2021 in São-Carlos, Brazil. Participants aged > 18 years, with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized (1:1) into two groups that received different treatments during a period of at-home-isolation. One group received the homeopathic medicine Natrum muriaticum, prepared with the second degree of the fifty-millesimal dynamization (LM2; Natrum muriaticum LM2), while the other group received a placebo. OUTCOME MEASURES: The primary endpoint was time until recovery from COVID-19 influenza-like symptoms. Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms (influenza-like symptoms plus anosmia and ageusia) from a symptom grading scale that was informed by the participant, hospital admissions, and adverse events. Kaplan-Meier curves were used to estimate time-to-event (survival) measures. RESULTS: Data from 86 participants were analyzed (homeopathy, n = 42; placebo, n = 44). There was no difference in time to recovery between two groups among participants who were reporting influenza-like symptoms at the beginning of monitoring (homeopathy, n = 41; placebo, n = 41; P = 0.56), nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring (homeopathy, n = 15; placebo, n = 17; P = 0.06). Secondary outcomes indicated that a 50% reduction in symptom score was achieved significantly earlier in the homeopathy group (homeopathy, n = 24; placebo, n = 25; P = 0.04), among the participants with a basal symptom score ≥ 5. Moreover, values of restricted mean survival time indicated that patients receiving homeopathy might have improved 0.9 days faster during the first five days of follow-up (P = 0.022). Hospitalization rates were 2.4% in the homeopathy group and 6.8% in the placebo group (P = 0.62). Participants reported 3 adverse events in the homeopathy group and 6 in the placebo group. CONCLUSION: Results showed that Natrum muriaticum LM2 was safe to use for COVID-19, but there was no statistically significant difference in the primary endpoints of Natrum muriaticum LM2 and placebo for mild COVID-19 cases. Although some secondary measures do not support the null hypothesis, the wide confidence intervals suggest that further studies with larger sample sizes and more symptomatic participants are needed to test the effectiveness of homeopathic Natrum muriaticum LM2 for COVID-19. TRIAL REGISTRATION: UMIN Clinical Trials Registry ID: JPRN-UMIN000040602.

Homeopathy for Covid-19 in Primary Care: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: To investigate the effectiveness and safety of homeopathic medicine Natrum muriaticum (LM2) for mild cases of COVID-19 in Primary Health Care. TRIAL DESIGN: A randomized, two-armed (1:1), parallel, placebo-controlled, double-blind, clinical trial is being performed to test the following hypotheses: H0: homeopathic medicines = placebo (null hypothesis) vs. H1: homeopathic medicines ≠ placebo (alternative hypothesis) for mild cases of COVID-19 in Primary Care. PARTICIPANTS: Setting: Primary Care of São Carlos - São Paulo - Brazil. One hundred participants aged 18 years or older, with Influenza-like symptoms and a positive RT-PCR for SARS-CoV-2. Willingness to give informed consent and to comply with the study procedures is also required. Exclusion criterium: severe acute respiratory syndrome. INTERVENTION AND COMPARATOR: Homeopathy: 1 globule of Natrum muriaticum LM2 diluted in 20 mL of alcohol 30% and dispensed in a 30 ml bottle. Placebo: 20 mL of alcohol 30% dispensed in a 30 ml bottle. Posology: one drop taken orally every 4 hours (6 doses/day) while there is fever, cough, tiredness, or pain (headache, sore throat, muscle aches, chest pain, etc.) followed by one drop every 6 hours (4 doses/day) until the fourteenth day of use. The bottle of study medication should be submitted to 10 vigorous shakes (succussions) before each dose. Posology may be changed by telemedicine, with no break in blinding. Study medication should be maintained during home isolation. According to the Primary Care protocol, the home isolation period lasts until the 10th day after the appearance of the first symptom, or up to 72 hours without symptoms. MAIN OUTCOMES: The primary endpoint will be time to recovery, defined as the number of days elapsed before all COVID-19 Influenza-like symptoms are recorded as mild or absent during home isolation period. Secondary measures are recovery time for each COVID-19 symptom; score of the scale created for the study (COVID-Simile Scale); medicines used during follow-up; number of days of follow-up; number of visits to emergency services; number of hospitalizations; other symptoms and Adverse Events during home isolation period. RANDOMISATION: The study Statistician generated a block randomization list, using a 1:1 ratio of the two groups (denoted as A and B) and a web-based tool ( http://www.random.org/lists ). BLINDING (MASKING): The clinical investigators, the statistician, the Primary Care teams, the study collaborators, and the participants will remain blinded from the identity of the two treatment groups until the end of the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): One hundred participants are planned to be randomized (1:1) to placebo (50) or homeopathy (50). TRIAL STATUS: Protocol version/date May 21, 2020. Recruitment is ongoing. First participant was recruited/included on June 29,2020. Due to recruitment adaptations to Primary Care changes, the authors anticipate the trial will finish recruiting on April 10, 2021. TRIAL REGISTRATION: COVID-Simile Study was registered at the University Hospital Medical Information Network (UMIN - https://www.umin.ac.jp/ctr/index.htm ) on June 1st, 2020, and the trial start date was June 15, 2020. Unique ID: UMIN000040602. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Double-blind evaluation of homeopathy on cocaine craving: a randomized controlled pilot study.

BACKGROUND: Brazil is among the nations with the greatest rates of annual cocaine usage. Pharmacological treatment of cocaine addiction is still limited, opening space for nonconventional interventions. Homeopathic Q-potencies of opium and Erythroxylum coca have been tested in the integrative treatment of cocaine craving among homeless addicts, but this setting had not proven feasible, due to insufficient recruitment. OBJECTIVE: This study investigates the effectiveness and tolerability of homeopathic Q-potencies of opium and E. coca in the integrative treatment of cocaine craving in a community-based psychosocial rehabilitation setting. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A randomized, double-blind, placebo-controlled, parallel-group, eight-week pilot trial was performed at the Psychosocial Attention Center for Alcohol and Other Drugs (CAPS-AD), Sao Carlos/SP, Brazil. Eligible subjects included CAPS-AD patients between 18 and 65 years of age, with an International Classification of Diseases-10 diagnosis of cocaine dependence (F14.2). The patients were randomly assigned to two treatment groups: psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca (homeopathy group), and psychosocial rehabilitation plus indistinguishable placebo (placebo group). MAIN OUTCOME MEASURES: The main outcome measure was the percentage of cocaine-using days. Secondary measures were the Minnesota Cocaine Craving Scale and 12-Item Short-Form Health Survey scores. Adverse events were reported in both groups. RESULTS: The study population comprised 54 patients who attended at least one post-baseline assessment, out of the 104 subjects initially enrolled. The mean percentage of cocaine-using days in the homeopathy group was 18.1% (standard deviation (SD): 22.3%), compared to 29.8% (SD: 30.6%) in the placebo group (P < 0.01). Analysis of the Minnesota Cocaine Craving Scale scores showed no between-group differences in the intensity of cravings, but results significantly favored homeopathy over placebo in the proportion of weeks without craving episodes and the patients' appraisal of treatment efficacy for reduction of cravings. Analysis of 12-Item Short-Form Health Survey scores found no significant differences. Few adverse events were reported: 0.57 adverse events/patient in the homeopathy group compared to 0.69 adverse events/patient in the placebo group (P = 0.41). CONCLUSIONS: A psychosocial rehabilitation setting improved recruitment but was not sufficient to decrease dropout frequency among Brazilian cocaine treatment seekers. Psychosocial rehabilitation plus homeopathic Q-potencies of opium and E. coca were more effective than psychosocial rehabilitation alone in reducing cocaine cravings. Due to high dropout rate and risk of bias, further research is required to confirm our findings, with specific focus on strategies to increase patient retention. TRIAL REGISTRATION: RBR-2xzcwz (http://www.ensaiosclinicos.gov.br).

Homeopathy for Perennial Asthma in Adolescents: Pilot Feasibility Study Testing a Randomised Withdrawal Design.

INTRODUCTION: Previous findings from a pragmatic trial suggest that usual care compared with usual care plus individualised homeopathy is not a feasible design to address homeopathic interventions for asthma. OBJECTIVE: The main purpose of this article was to investigate the feasibility of the randomised withdrawal design as a strategy to assess the effectiveness of a standardised clinical-pharmaceutical homeopathic protocol (Organon.modus) on perennial asthma in adolescents. METHODS: Randomised withdrawal, double-blind, parallel, placebo-controlled, 12-week study. Patients: 12 to 17 years old adolescents, with the diagnosis of perennial asthma, using inhalatory beclomethasone (plus fenoterol for wheezing episodes), who achieved 3 months of well-controlled asthma, after a variable period of individualised homeopathic treatment according to Organon.modus protocol. Setting: a secondary care medical specialist centre. Intervention: continuation with the individualised homeopathic medicine or with indistinguishable placebo during 12 weeks of beclomethasone step-down. Primary outcome: number of days of well-controlled asthma. Secondary measures: number of days of fenoterol use, number of visits to an emergency service (without hospitalisation) and percentage of patients excluded due to an exacerbation characterising a partly controlled asthma. Tolerability was assessed by Adverse Events, registered at every visit. RESULTS: Nineteen patients were randomised to continue treatment with homeopathy and 21 with placebo. Effectiveness measures for the homeopathy and placebo groups respectively were median number of days of good clinical control: 84 versus 30 (p = 0.18); median number of days of fenoterol use per patient: 3 versus 5 (p = 0.41); visits to an emergency room: 1 versus 6 (p = 0.35); percentage of exclusion due to partly controlled asthma: 36.8% versus 71.4% (p = 0.05). Few Adverse Events were reported. CONCLUSIONS: This pilot study supports the feasibility of the double-blind randomised withdrawal design in studies investigating homeopathy on teenage asthma, when performed by specialists following a standardised clinical-pharmaceutical homeopathic protocol. CLINICAL TRIAL REGISTRATION: RBR-6XTS8Z.