Fast pain relief in exercise-induced acute musculoskeletal pain by turmeric-boswellia formulation: A randomized placebo-controlled double-blinded multicentre study.

BACKGROUND: Plant extracts with analgesic properties are seldom considered for treatment of acute musculoskeletal pain due to delay in onset of analgesia. Turmeric (Curcuma longa) and boswellia (Boswellia serrata) extracts are well-studied anti-inflammatory compounds gaining in popularity and used as an alternative to conventional treatments for musculoskeletal pain. This study analyzed the analgesic effect of a formulation of turmeric and boswellia extracts in sesame oil (Rhuleave-K, TBF) in reducing exercise-induced acute musculoskeletal pain in healthy participants. METHODS: In this randomized double-blinded placebo-controlled, single-dose, single-day, multicentre study, a total of 232 participants (TBF n = 116; placebo n = 116) having moderate-to-severe exercise-induced acute musculoskeletal pain were randomized in an allocation concealed 1:1 ratio to receive a single dose of 1000 mg of TBF or placebo. The outcome measures were numerical rating scale (NRS), categorical pain relief scale (PRS), onset of analgesia, and short form of McGill questionnaire (SF-MPQ). NRS and PRS were measured from predose to every 30 minutes interval of postdose up to 6 hours at rest, with movement and applying pressure on the affected part. The onset of analgesia was measured from the time of dosage and censored at 6 hours of postdose. The sum of pain intensity difference (SPID6) and total pain relief (TOTPAR6) at 6 hours was, respectively, analyzed from NRS and PRS scores. RESULTS: TBF showed a significant reduction in pain intensity (SPID6rest) with 97.85% improvement in cumulative responder analysis compared with 2.46% in placebo. The onset of pain relief was fast and highly significant in the TBF group with 99% of participants having a mean perceptible pain relief at 68.5 minutes (95% confidence interval, 59.5-77.4) and 96% of participants having a mean meaningful pain relief at 191.6 minutes (95% confidence interval, 176.7-206.4) compared to the placebo group. Highly significant and continuous improvement in pain relief was observed in the TBF group with 93% of participants having ≥ 50% of maximum TOTPAR6 with a number needed to treat of 1.1 at rest. CONCLUSION: Exercise-induced acute musculoskeletal pain can be effectively relieved by TBF (Rhuleave-K) in about 3 hours signifying its strong analgesic activity.

Immunogenicity and safety of two quadrivalent influenza vaccines in healthy adult and elderly participants in India - A phase III, active-controlled, randomized clinical study.

BACKGROUND: This study was conducted to compare the immunogenicity and safety profile of two quadrivalent influenza vaccines (QIVs) in healthy adults (18-60 years) and elderly (>61 years) participants. METHOD: This phase III study was conducted from March 2018 to April 2018 across 12 sites in India. In this randomized, observer-blind, active-controlled study, 480 participants were randomized to receive a single dose of test vaccine (subunit, inactivated influenza vaccine; Influvac® Tetra, Abbott) (n = 240) or reference vaccine (split virion, inactivated influenza vaccine; VaxiFlu-4, Zydus Cadilla Healthcare) (n = 240). The primary objective was to describe and compare the immunogenicity of each vaccination group based on hemagglutination inhibition (HI) assay seroprotection and seroconversion rates, and geometric mean fold increase (GMFI) against four vaccine strains in two age groups. Safety and reactogenicity were also compared for the vaccines in both the age groups. RESULTS: The pre- and post-vaccination HI titers for both the vaccines were comparable. The GMFI varied from 4.3 - 22.7 in the test and 3.7-21.6 in the reference vaccine group. The seroprotection rates were >90% for the A-strains and ranged between >43% and <60% for B-strains for both the vaccines. Seroconversion rates varied between 41.4% and 78.8%. Overall, the reported adverse events (AEs) for both the vaccines were <1% and comparable. Reported local and systemic reactions were comparable. CONCLUSION: Influvac® Tetra elicited an adequate immune response with a favorable safety profile which was comparable with the reference vaccine. (Clinical trial registry number: CTRI/2018/02/012222).

Sociodemographic and Clinical Profiles of Patients with Irritable Bowel Syndrome: A Cross-sectional, Multi-centric, Epidemiological Study in India.

AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by impaired gut-brain interaction. Considering the paucity of evidence in the Indian setting, the current study was conducted to determine the sociodemographics, clinical profiles, management practices, and patients' perception among newly diagnosed patients with IBS. METHODS: This was a cross-sectional, single-visit, observational, non-interventional, epidemiological study conducted across 12 centres. The primary objective was evaluation of sociodemographic and clinical profiles. The key secondary objective was assessment of gastrointestinal symptom severity including evaluation of anxiety and depression using the hospital anxiety and depression scale (HADS) scores. Knowledge, attitude, and practices (KAP) were evaluated as an exploratory objective. RESULTS: Out of 300 enrolled patients, 120 (40%) were aged 31-45 years (mean age: 38.55±12.45 years), and 204 were men (68%). Overall, 40% of patients belonged to the upper-middle-class, with a Kuppuswamy score of 16-25. Most patients (91%) did not work in night shifts. Only 13% of patients performed more than recommended physical activity. Stress and food were the leading triggers for IBS (29%). Abdominal pain and diarrhoea as cardinal symptoms were reported by 43.3% and 33.0% patients, respectively. Borderline abnormal anxiety and depression were reported by 21.3% and 26.7% of patients, respectively. KAP assessment revealed that 56.0% of patients had poor knowledge, 26.3% had moderate knowledge, and 17.7% had good knowledge about IBS; nevertheless, 43% of patients maintained high levels of precaution towards managing symptoms. CONCLUSION: Given the limited knowledge about IBS in India among newly diagnosed patients, strategies to enhance awareness about the condition are warranted.

Efficacy and safety of evogliptin versus sitagliptin as an add-on therapy in Indian patients with type 2 diabetes mellitus inadequately controlled with metformin: A 24-week randomized, double-blind, non-inferiority, EVOLUTION INDIA study.

AIM: This study aimed to assess efficacy and safety of evogliptin versus sitagliptin, when added to background metformin therapy in Indian patients with uncontrolled type 2 diabetes. METHOD: Overall, 184 patients with uncontrolled type 2 diabetes (7% ≤ HbA1c < 10%) receiving ≥8 weeks of stable metformin monotherapy (≥1 g/day), were randomized to receive add-on treatment (evogliptin 5 mg or sitagliptin 100 mg) for 24 weeks. Primary endpoint was change in HbA1c from baseline to 12 weeks (non-inferiority margin: <0.35). RESULTS: Mean reductions in HbA1c at 12 weeks in evogliptin- and sitagliptin-treated patients were -0.37 (1.06) and -0.32 (1.14), respectively. The adjusted mean difference between treatment groups was -0.022 (95% CI: -0.374, 0.330; P = 0.901), that demonstrated non-inferiority. Reductions in FPG and PPG were similar between evogliptin and sitagliptin at 12 and 24 weeks. Changes in body weight were comparable between the treatment groups. Patients achieving target HbA1c < 7.0% (evogliptin, 26.7% vs. sitagliptin, 20%) was almost equal in both groups. Treatment-emergent adverse events occured in 52 patients (evogliptin, 25% and sitagliptin, 31.5%) and were generally mild. CONCLUSIONS: Evogliptin was non-inferior to sitagliptin in HbA1c reduction. It effectively improved glycemic control and was well tolerated in type 2 diabetes patients inadequately controlled by metformin alone.

Efficacy and Safety of Intravenous Tenecteplase Bolus in Acute Ischemic Stroke: Results of Two Open-Label, Multicenter Trials.

BACKGROUND: Tenecteplase (TNK-tPA) is a promising third-generation plasminogen activator, because of its greater fibrin specificity and longer half-life than alteplase. There is a paucity of studies on intravenous thrombolysis using TNK-tPA in developing countries. The present study has been undertaken to compare the efficacy and safety of TNK-tPA with alteplase. METHODS: Two studies were conducted. Study I was an open-label, randomized study in which two doses of TNK-tPA (0.1 and 0.2 mg/kg) were compared. Study II was an open-label study in which TNK-tPA 0.2 mg/kg bolus was compared with historical controls. The primary endpoint for study I and study II was an improvement of ≥ 8 points or a score of 0 on the National Institutes of Health Stroke Scale (NIHSS) [major neurological improvement (MNI)] at 24 h. Secondary endpoints for both studies were neurological improvement as assessed using the NIHSS score, modified Rankin Scale (mRS) score and the Barthel Index (BI) on days 7, 30 and 90. Minimal disability was defined as an mRS score of 0 or 1 and good functional recovery as a BI score of 50-90. Safety was assessed by the proportion of patients having symptomatic intracranial hemorrhage (sICH) within 36 h and asymptomatic intracranial hemorrhage at 48 h after treatment. RESULTS: In study I, 20 patients received 0.1 mg/kg and 30 received 0.2 mg/kg TNK-tPA. There was no significant difference in MNI at 24 h between 0.1 and 0.2 mg/kg TNK-tPA doses. The patients given 0.2 mg/kg TNK-tPA had a significantly better 3-month outcome (minimal disability, p = 0.007). There was no sICH in study I. In study II, 62 patients (one lost to follow-up) received 0.2 mg/kg TNK-tPA. MNI was noted in ten patients (16.4%), 3-month minimal disability was noted in 37 patients (60.7%), and good functional recovery was seen in 33 patients (54.1%). sICH occurred in one patient, and four patients died. Pooled data of patients in study I and study II receiving 0.2 mg/kg TNK-tPA were compared with data from the historical National Institute of Neurological Disorders and Stroke (NINDS) trial. For comparison, the primary endpoint of the NINDS trial (improvement on NIHSS of ≥ 4 points or a score of 0 at 24 h) was taken. The primary endpoint though was not significantly different (58.2% vs. 47%, p = 0.08), but with TNK-tPA, greater neurological improvement, minimal disability (70.3 vs. 39%, p < 0.001) and good functional recovery (36.3 vs. 16%, p < 0.001) was noted at 3 months. There was a lower incidence of sICH (1.1 vs. 6.4%, p = 0.05) and lower 3-month mortality (5.5 vs. 17%, p = 0.01) noted with TNK-tPA compared with alteplase. CONCLUSIONS: Intravenous TNK-tPA 0.2 mg/kg administered within 3 hours of symptom onset seems to be well tolerated and effective option in patients with acute ischemic stroke. TRIAL REGISTRATION: Clinical Trials Registry-India, www.ctri.nic.in ; unique identifiers: CTRI/2009/091/000251 and CTRI/2015/02/005556.

Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial.

BACKGROUND: Subclinical hypothyroidism, a thyroid disorder without obvious symptoms of thyroid deficiency, occurs in 3%-8% of the global population. Ashwagandha [Withania somnifera (L.) Dunal], a traditional medicine in Ayurveda, is often prescribed for thyroid dysfunctions. OBJECTIVE: This pilot study was designed to evaluate the efficacy and safety of ashwagandha root extract in subclinical hypothyroid patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized, double-blind, single-center placebo-controlled study was performed at Sudbhawana Hospital, Varanasi, India between May 2016 and September 2016. Fifty subjects with elevated serum thyroid stimulating hormone (TSH) levels (4.5-10 µIU/L) aged between 18 and 50 were randomized in either treatment (n = 25) or placebo (n = 25) groups for an 8-week treatment period. INTERVENTIONS: Ashwagandha root extract (600 mg daily) or starch as placebo. Efficacy Variables: Serum TSH, serum triiodothyronine (T3), and thyroxine (T4) levels. RESULTS: A total of four subjects (two from each group) withdrew their consent before the second visit. Eight weeks of treatment with ashwagandha improved serum TSH (p < 0.001), T3 (p = 0.0031), and T4 (p = 0.0096) levels significantly compared to placebo. Ashwagandha treatment effectively normalized the serum thyroid indices during the 8-week treatment period in a significant manner (time-effects: TSH [p < 0.001], T3 [p < 0.001], and T4 [p < 0.001]). Four subjects (8%) (ashwagandha: 1[4%]; Placebo: 3[12%]) out of 50 reported few mild and temporary adverse effects during this study. CONCLUSION: Treatment with ashwagandha may be beneficial for normalizing thyroid indices in subclinical hypothyroid patients.

A Multicentre, Open label, Randomized, Comparative, Parallel Group, Active-controlled, Phase III Clinical Trial to Evaluate Safety and Efficacy of Arbekacin Sulphate Injection versus Vancomycin Injection in Patients Diagnosed with MRSA Infection.

BACKGROUND: Increasing resistance to currently available antimicrobials has led to the development of new agents. Arbekacin is aminoglycoside antibiotic currently used in Japan and Korea for the treatment of infections caused by multi-resistant bacteria including MRSA. Currently there is no published data available for use of Arbekacin in Indian patient population, thus the present study was conducted to evaluate the safety and efficacy of Arbekacin in Indian population. MATERIAL AND METHODS: The study was a phase III, multi-centre, open-label, randomised comparative, active control study. Subjects with microbiologically confirmed MRSA infection were randomized in the study to receive either Arbekacin sulphate 200 mg OD or Vancomycin hydrochloride 1000 mg BD for a period of 7 to 14 days. The primary endpoint was to evaluate the overall cure rate i.e. Clinical and microbiological cure during the study. RESULTS: A total of 162 patients were randomized in 2 treatment groups (i.e. 81 patients in each group). Out of these microbiologically confirmed MRSA patients, 153 patients were admitted for SSTI while 9 patients were admitted for CAP. Overall cure rate of MRSA infection (clinical as well as microbiological cure) was comparable in both the treatment groups i.e. 97.5% (79/81) in Arbekacin group and 100 % (79/79) in Vancomycin group (p value: 0.159). Both Arbekacin and Vancomycin were well tolerated by the patients during the study period. CONCLUSION: Arbekacin can be considered as safe and effective alternative to vancomycin in the management of MRSA infections.