Efficacy and Safety of Levamisole Treatment in Clinical Presentations of Patients With COVID-19: A Double-Blind, Randomized, Controlled Trial

Abstract BackgroundIn late December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified as the cause of a series of pneumonia cases in China. Levamisole can show clinical benefits in management of COVID-19 by its immunomodulatory effect, but effect in clinical status of patients is unknown. We evaluated the efficacy of levamisole on clinical status of patients with COVID-19 on days 3, 7, and 14.MethodsThis prospective, double-blind, randomized, and controlled clinical trial was performed in 18- to 60-year-old patients with confirmed COVID-19 from late April 2020 to mid-August 2020. Patients were randomly assigned to two groups to receive a 5-day course of levamisole or placebo in combination with routine care. Results50 patients with COVID-19 were analyzed: 25 patients were in each group. More than half of the infected patients was men too (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution compared with Placebo (P=0.034 and 0.005, respectively). The difference in fever status on days 1, 3, 7, and 14 between two groups was not statistically significant (P > 0.05). There was significant differences between two groups in dyspnea over a median follow-up of 7th (P=0.015) and 14th (P=0.010) days after receiving the interventions. ConclusionThe results of the current study have overall demonstrated that patients receiving levamisole had significantly higher odds of having a better clinical status including cough and Dyspnea on day 14 than those receiving placebo, but with an effect-size of unsure clinical importance. The difference in the distribution of fever on days 3, 7, and 14 between two groups was not significant, suggesting that levamisole can efficiently improve the most clinical status of patients with COVID-19 infectious compared to placebo.Trial registrationThe trial was registered as IRCT20190810044500N7 (19/09/2020).

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Efficacy and safety of Levamisole treatment in clinical presentations of non-hospitalized patients with COVID-19: a double-blind, randomized, controlled trial

BMC Infectious Diseases ◽

10.1186/s12879-021-05983-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Amirreza Roostaei Firozabad ◽

Zohreh Akhoundi Meybodi ◽

Seyed Ruhollah Mousavinasab ◽

Adeleh Sahebnasagh ◽

Mohsen Gholinataj Jelodar ◽

...

Keyword(s):

Controlled Trial ◽

Clinical Status ◽

Clinical Importance ◽

Standard Of Care ◽

Controlled Clinical Trial ◽

Double Blind ◽

Randomized Controlled ◽

Significant Difference ◽

Clinical Benefits ◽

Study Participants

Abstract Background Levamisole has shown clinical benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clinical status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clinical status of patients with COVID-19 during their course of the disease. Methods This prospective, double-blind, randomized controlled clinical trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late April 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care. Results With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, respectively). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05). Conclusion The results of the current study suggest that Levamisole may improve most of clinical status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clinical status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clinical importance. Trial registration The trial was registered as IRCT20190810044500N7 (19/09/2020).

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A double-blind randomized controlled trial of topical Curcuma xanthorrhiza Roxb. on mild psoriasis: clinical manifestations, histopathological features, and K6 expressions

Medical Journal of Indonesia ◽

10.13181/mji.v27i3.2511 ◽

2018 ◽

Vol 27 (3) ◽

pp. 178-84 ◽

Cited By ~ 1

Author(s):

Githa Rahmayunita ◽

Tjut N.A. Jacoeb ◽

Endi Novianto ◽

Wresti Indriatmi ◽

Rahadi Rihatmadja ◽

...

Keyword(s):

Controlled Trial ◽

Clinical Manifestations ◽

Effective Treatment Option ◽

Psoriasis Area Severity Index ◽

Double Blind ◽

Old Patients ◽

Mean Values ◽

Significant Difference ◽

Curcuma Xanthorrhiza ◽

The Difference

Background: Curcuma xanthorrhiza Roxb. exerts its anti-inflammatory effects by reducing the concentration of IL-6, IL-8, and phosphorylase kinase, which has role in keratinocyte proliferation. Our study aimed to evaluate the efficacy of C. xanthorrhiza in psoriasis.Methods: From 18 to 59 year-old patients with mild psoriasis, 2 similar lesions were selected. The severity assessment was based on the psoriasis area severity index (PASI), Trozak score, and K6 expression. Using a double-blinded randomized method, lesion was treated with 1% C. xanthorrhiza ointment vs placebo for 4 weeks. The results were analyzed by the chi-square test using STATATM V.12 software (Stata Corp.).Results: The study was conducted in 2010 to 2012 with 17 subjects participated. The median of PASI score were reduced significantly in both lesions, either treated with 1% C. xanthorrhiza ointment vs placebo; however when compared between the group, it was not significant (p=0.520). The Trozak score were reduced in lesions treated with 1% C. xanthorrhiza ointment; but it was not significant (p = 0.306). In lesions treated with placebo, the Trozak score was increased significantly. The difference of Trozak score between lesions treated with C. xanthorrhiza and placebo was significant (p=0.024). There was no significant difference of K6 expression in lesions treated with 1% C. xanthorrhiza ointments or placebo as well as on the difference of mean values of K6 expression between the group (p=0.827).Conclusion: Based on the results, 1% C. xanthorrhiza ointment is effective treatment option for mild psoriasis, but longer follow-up period is suggested to confirm this results. C. xanthorrhiza ointment is safe for topical administration as there were no side effects reported in this study.

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A Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Trial of O-(β-Hydroxyetnyl)-Rutosides in Chronic Arm Oedema Resulting from Breast Cancer Treatment

Phlebology The Journal of Venous Disease ◽

10.1177/026835559501000204 ◽

1995 ◽

Vol 10 (2) ◽

pp. 51-55 ◽

Cited By ~ 10

Author(s):

P. S. Mortimer ◽

C. Badger ◽

I. Clarke ◽

J. Pallett

Keyword(s):

Breast Cancer ◽

Controlled Trial ◽

Symptom Assessment ◽

Controlled Clinical Trial ◽

Point Scale ◽

Carcinoma Of The Breast ◽

Double Blind ◽

Parallel Group ◽

Royal Marsden Hospital ◽

The Difference

Objective: To assess the efficacy of O-(β-hydroxyethyl)-rutosides (HR) in the treatment of breast-cancer-related lymphoedema. Design: A double-blind, randomized, parallel-group, placebo-controlled clinical trial. Setting: Lymphoedema clinic, Royal Marsden Hospital, London, UK. Patients: Forty-six females with unilateral lymphoedema of the arm secondary to therapy for carcinoma of the breast. Main outcome measures: Arm volume, symptom assessment on a five-point scale. Results: The difference in arm volumes was significantly better for HR than placebo at 6 months, but not at 1–5 months. Conclusion: HR appears to stabilize the patients' condition against increasing lymphoedema in the placebo group.

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A multi-centre, randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir for the treatment of COVID-19 in Lagos State: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05675-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

A. Abayomi ◽

A. Osibogun ◽

O. Ezechi ◽

K. Wright ◽

B. Ola ◽

...

Keyword(s):

Controlled Trial ◽

Clinical Status ◽

Standard Of Care ◽

World Health ◽

Ordinal Scale ◽

Controlled Clinical Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Research Participants ◽

Lagos State

Abstract Background The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in Wuhan, Hubei, China, in December 2019. It was recognized as a pandemic by the World Health Organization on 11 March 2020. Outbreak forecasting and mathematical modelling suggest that these numbers will continue to rise. Early identification of effective remedies that can shorten the duration and severity of illness is critical for Lagos State, which is the epi-centre of the disease in Nigeria. Methods This is a multi-centre, randomized, double-blind placebo-controlled superiority trial. The study investigates the efficacy of chloroquine phosphate, hydroxychloroquine sulphate and lopinavir/ritonavir added on to standard of care compared to standard of care only in patients with COVID-19 disease. The primary outcome is the clinical status of patients measured using a 7-point ordinal scale at day 15. Research participants and clinicians will be blinded to the allocated intervention. Outcome measures will be directly assessed by clinicians. Statistical analysis will be done by a team blinded to the identity and allocation of research participants. Data analysis will follow intention-to-treat methods, using R software. Discussion The current study is of strategic importance for Lagos State in potentially curbing the health, social and economic burden of COVID-19 disease. Should the current study demonstrate that either of the three intervention drugs is more efficacious than standard therapy alone, the State Ministry of Health will develop an evidence-based guideline for the management of COVID-19 in Lagos State. The findings will also be shared nationally and with other states which may lead to a standardized national guideline for the treatment of COVID-19 in Nigeria. Trial registration Pan African Clinical Trials Register PACTR202004801273802. Registered prospectively on April 2, 2020

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Sofosbuvir and daclatasvir for the treatment of COVID-19 outpatients: a double-blind, randomized controlled trial

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa501 ◽

2020 ◽

Cited By ~ 1

Author(s):

Fatemeh Roozbeh ◽

Majid Saeedi ◽

Reza Alizadeh-Navaei ◽

Akbar Hedayatizadeh-Omran ◽

Shahin Merat ◽

...

Keyword(s):

Controlled Trial ◽

Controlled Clinical Trial ◽

Double Blind ◽

Randomized Controlled ◽

Number Of Patients ◽

Significant Difference ◽

The Difference ◽

Novel Coronavirus ◽

Loss Of Appetite

Abstract Introduction Effective treatments are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection. Methods This was a randomized controlled clinical trial in outpatients with mild COVID-19. Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. The primary endpoint of the trial was symptom alleviation after 7 days of follow-up. The secondary endpoint of the trial was hospital admission. Fatigue, dyspnoea and loss of appetite were investigated after 1 month of follow-up. This study is registered with the IRCT.ir under registration number IRCT20200403046926N1. Results Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms at Day 7. One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001. Conclusions In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month. Larger, well-designed trials are warranted.

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Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05253-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Aziza Ajlan ◽

Hassan Aleid ◽

Tariq Zulfiquar Ali ◽

Hala Joharji ◽

Khalid Almeshari ◽

...

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Controlled Trial ◽

Controlled Clinical Trial ◽

First Year ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Double Blind ◽

Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

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A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00795-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Shifu Xiao ◽

Piu Chan ◽

Tao Wang ◽

Zhen Hong ◽

Shuzhen Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trial ◽

Controlled Trial ◽

Drug Effects ◽

Disease Assessment ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo ◽

The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

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Effect of antenatal dietary myo-inositol supplementation on the incidence of gestational diabetes mellitus and fetal outcome: protocol for a double-blind randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2021-055314 ◽

2022 ◽

Vol 12 (1) ◽

pp. e055314

Author(s):

Ibrahim Ibrahim ◽

Hala Abdullahi ◽

Yassin Fagier ◽

Osman Ortashi ◽

Annalisa Terrangera ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Controlled Trial ◽

Tolerance Test ◽

Dietary Advice ◽

Controlled Clinical Trial ◽

Oral Glucose ◽

Double Blind ◽

Registration Number

IntroductionGestational diabetes mellitus (GDM) affects 23.6% of Qatari women and is associated with maternal and perinatal morbidity and long-term risk of developing type 2 diabetes. A number of challenges exist with current interventions, including non-compliance with dietary advice, the reluctance of mothers to ingest metformin tablets or use insulin injections. These challenges highlight the importance of pursuing evidence-based prevention strategies. Myo-inositol is readily available as an US Food and Drug Administration-approved food supplement with emerging but limited evidence suggesting it may be beneficial in reducing the incidence of GDM. Further studies, such as this one, from different ethnic contexts and with differing risk factors, are urgently needed to assess myo-inositol effects on maternal and neonatal outcomes.Methods and analysisThis study is a prospective, randomised, double-blinded, placebo controlled clinical trial to either myo-inositol supplementation or placebo.We plan to enrol 640 pregnant women attending antenatal care at Sidra Medicine, Doha, Qatar, 320 in each arm. All participants will complete at least 12 weeks of supplementation prior to undertaking the Oral Glucose Tolerance Test at 24–28 weeks. The daily use of the trial supplementation will continue until the end of pregnancy. All outcome measures will be collected from the electronic medical records.Ethics and disseminationEthical approval for the study was obtained on 12 April 2021 from Sidra Medicine (IRB number 1538656). Results of the primary trial outcome and secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration numberProspectively registered on 26 May 2021. Registration number ISRCTN16448440 (ISRCTN registry).

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Mirror therapy for phantom limb and stump pain: a randomized controlled clinical trial in landmine amputees in Cambodia

Scandinavian Journal of Pain ◽

10.1515/sjpain-2018-0042 ◽

2018 ◽

Vol 18 (4) ◽

pp. 603-610 ◽

Cited By ~ 4

Author(s):

Ha Sam Ol ◽

Yang Van Heng ◽

Lena Danielsson ◽

Hans Husum

Keyword(s):

Low Income ◽

Controlled Trial ◽

Phantom Limb Pain ◽

Phantom Limb ◽

Controlled Clinical Trial ◽

Mirror Therapy ◽

Randomized Controlled ◽

Stump Pain ◽

The Difference ◽

Therapy Interventions

Abstract Background and aims The aim of the study was to examine the effect of mirror and tactile therapy on phantom and stump pain in patients with traumatic amputations, with particular reference to amputees in low-income communities. Methods The study was conducted with an open, randomized, semi-crossover case-control design in rural Cambodia. A study sample of 45 landmine victims with trans-tibial amputations was allocated to three treatment arms; mirror therapy, tactile therapy, and combined mirror-and-tactile therapy. Non-responders from the mono-therapy interventions were crossed over to the alternative intervention. The intervention consisted of 5 min of treatment every morning and evening for 4 weeks. Endpoint estimates of phantom limb pain (PLP), stump pain, and physical function were registered 3 months after the treatment. Results All three interventions were associated with more that 50% reduction in visual analogue scale (VAS)-rated PLP and stump pain. Combined mirror-tactile treatment had a significantly better effect on PLP and stump pain than mirror or tactile therapy alone. The difference between the three treatment arms were however slight, and hardly of clinical relevance. After treatment, the reduction of pain remained unchanged for an observation period of 3 months. Conclusions The study documents that a 4-week treatment period with mirror and/or tactile therapy significantly reduces PLP and stump pain after trans-tibial amputations. Implications The article reports for the first time a randomized controlled trial of mirror therapy in a homogenous sample of persons with traumatic amputations. The findings are of special relevance to amputees in low-resource communities.

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Antithrombin Therapy for Severe Preeclampsia

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614071 ◽

2000 ◽

Vol 84 (10) ◽

pp. 583-590 ◽

Cited By ~ 42

Author(s):

Masahiro Maki ◽

Toshihiko Terao ◽

Tsuyomu Ikenoue ◽

Kazuo Satoh ◽

Masao Nakabayashi ◽

...

Keyword(s):

Weight Gain ◽

Perinatal Outcome ◽

Controlled Trial ◽

Severe Preeclampsia ◽

Fetal Weight ◽

Low Birth Weight Infants ◽

Double Blind ◽

Biophysical Profile ◽

The Difference ◽

Estimated Fetal Weight

SummaryA double-blind, randomized, placebo-controlled trial was conducted to evaluate whether treatment with Antithrombin (AT) concentrates improved the clinical and perinatal outcome in patients with severe preeclampsia. Severe preeclamptic patients (24 to 35 weeks of gestation, Gestosis Index (GI) > 6 points) were randomized into two groups: 66 received AT and 67 received placebo. There were no statistical differences in the clinical profiles of the two groups. Study drugs were given intravenously once daily for 7 consecutive days. Maternal symptoms were evaluated from the difference of GI between before and after treatment, and fetal findings were evaluated from the changes of the biophysical profile score and the estimated fetal weight gain. Improvement was significantly greater in the AT group for both the GI (p = 0.020) and the estimated fetal weight gain (p = 0.029). The improvement of coagulation parameters was also evaluated. The D-dimer levels increased significantly in the placebo group (p = 0.026), but did not change in the AT group. Gestation was significantly prolonged (p = 0.007), and the number of low-birth weight infants was significantly smaller (p = 0.011) in the AT group. No adverse events related to AT were observed. It is revealed that AT concentrate therapy for preeclampsia is effective and safe, leading to an improved perinatal outcome.

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