Efficacy and safety of polyherbal formulation as an add-on to standard-of-care in mild-to-moderate COVID-19: A randomized, double-blind, placebo-controlled trial.

Background: Novel corona virus disease-2019 (COVID-19) pandemic is a significant contributor to morbidity and mortality in affected individuals. Modulating the immune response in COVID-19 is now an established treatment approach. Polyherbal formulations have long been assessed for their potential immune modulating effects and are expected to be beneficial on COVID-19. Methods: This study aims at assessing the efficacy and safety of polyherbal formulation (referred as IP) in comparison to placebo, as add on to the standard of care (SOC), in patients with mild to moderate COVID-19 patients. Hospitalized RT-PCR positive patients were randomized to either SOC + IP or SOC + Placebo arm. The viral load (VL) was assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Immunological parameters were also assessed. The clinical improvement was assessed using a numeric rating scale (NRS) and WHO ordinal scale, and follow-up period was 30 days. Results: Seventy-two patients were randomized to SOC + IP (n = 39) and SOC + Placebo (n = 33) arms. There was significant reduction in VL in SOC + IP arm from day 0-4 (p = 0.002), compared to SOC + Placebo arm (p = 0.106). Change in the NRS score and WHO score was significant in both arms, however, the difference between the two arms was statistically significant in favour of IP arm. The increase in Th1 response was significant in SOC + IP arm (p = 0.023), but not in SOC + Placebo arm. COVID-19 specific antibodies were numerically higher in the SOC + IP arm. Conclusion: The study finds that polyherbal formulation significantly reduces VL and contributes to immunomodulation and improvement in clinical conditions without side effects.

Safety and efficacy of herbal extracts to restore respiratory health and improve innate immunity in COVID-19 positive patients with mild to moderate severity: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Primary Objective • To assess the efficacy of herbal extracts in boosting innate immunity of patients with COVID-19 infection. Secondary Objectives • To assess the efficacy of herbal extracts in restoring respiratory health • To assess the efficacy of Cap. IP in early recovery of patients and decline in viral load • To assess the safety of herbal extracts TRIAL DESIGN: This is a single centre, randomized, 2-arm, parallel group, double blind, 1:1 ratio, controlled, exploratory trial with a study period of 30 days from the day of enrolment. PARTICIPANTS: Patients attending the COVID treatment centre at Yashwantrao Chavan Memorial Hospital, Nehrunagar, Pimpri, Pune, India were screened for their participation in the study. Patients who were known COVID-19 positive (with positive RT-PCR), eligible and willing were enrolled in the study. INTERVENTION AND COMPARATOR: The intervention in the trial has a background in 'Ayurved'. Intervention Arm: Two capsules, Investigational Product (IP) - 1 - 400mg and Investigational Product - 2 - 450mg, containing herbal extracts (a blend of water and CO2 extracts) of Shunthi (Zingiber officinale (Ginger), Vidanga (Embelia ribes), Yashtimadhu (Glycyrrhiza glabra), Haritaki (Terminalia chebula), Guduchi (Tinospora cordifolia), Shatavari (Asparagus racemosus), Aamalaki (Emblica officinalis), Pippali (Piper longum) and calcined Zinc, Shankha bhasma. Placebo Arm: Edible starch ~ 450 mg. The look and feel of IP and of Placebo boxes were very similar. Patients are to take two capsules (one each of IP-1 and IP-2) twice a day for 15 days, and from the 16th day, one capsule of IP-2 twice a day up-to day 30. Capsules are to be administered orally with plain water. The IP is to be taken with all other concomitant medicines prescribed by the treating physician/doctor. The dose of each component in the IP is very safe to administer. The investigational products are registered products with the Indian Government and have been used for more than 6 months in various health conditions but not for COVID-19. MAIN OUTCOMES: Primary Outcome: Efficacy of the herbal extracts in COVID 19 positive patients (in declining viral load: time-point: 4 days and early recovery) Secondary Outcomes: Efficacy of the herbal extracts as an immune-modulator - TH1, TH2, Th17, IL6, NK Cells and CD markers; Immunoglobulin IGG (Serum); Immunoglobulin IGM (Serum) - at 30 days. Efficacy of the investigational product in reducing sequela of the disease Safety analysis (Liver Function Test and Kidney Function Test) including serious allergic reaction of: rash, itching/swelling, severe dizziness, trouble breathing. RANDOMISATION: An alphanumeric coded set of IP/Placebo containers will be used. Participants will be automatically randomized to two groups in the ratio 1:1. BLINDING (MASKING): Participants, caregivers and investigators were blinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of more than 60 and up to 75 patients were to be enrolled in the study into the two groups, considering drop-outs. 72 were enrolled with 37 into the intervention group and 35 into the placebo group. TRIAL STATUS: Protocol number: CoviQuest-01 Protocol version number: 1.2 Protocol Date: 1st July 2020 The recruitment period is completed for the trial. Date of 1st patient enrolment was 11th Aug 2020 and the last patient was enrolled on 3rd of September 2020. This is to state that it was a late submission from authors for publication of the protocol to the BMC, after enrolment in the study was over. Last Participant's last follow-up is scheduled on 5th October 2020 TRIAL REGISTRATION: The trial was prospectively registered with the CTRI (Clinical Trial Registry of India). Registration number is CTRI/2020/07/026570 . Registered on 14 July 2020 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.

Efficacy of Herbmed Plus in urolithic rats: An experimental study.

BACKGROUND: In Ayurveda, several herbs and formulations are available for the treatment of Urolithiasis. However, they are not systematically evaluated for their safety, efficacy, indication and limitations. Herbmed Plus is one such herbal formulation that has been known for the management of urinary tract disorders. An attempt has been made to evaluate its efficacy on Urolithiasis. OBJECTIVE: To evaluate the efficacy and safety of Herbmed Plus in urolithic rats. MATERIALS AND METHODS: A total of 60 Wistar albino rats were used for this study. The male and female rats were divided into five groups: disease control, test (dose 90 mg/kg), standard I (Cystone), standard II (Alkaston insta) and normal control (six in each group). Urolithiasis was induced using ethylene glycol 0.75% in drinking water for 28 days. The rats with urinary oxalate crystals were dosed with oral test or standard treatments for 28 days. RESULTS: All the animals appeared normal and showed no clinical signs of toxicity. None of the groups reported mortality or adverse effect on body weight and food consumption. The treatment with test drug showed improvement in the SGPT level and urine output (5.4 vs 3.47 mL/24 h). A drastic reduction in number of crystals were observed in male 0.5 vs 22 and female rats 0 vs 22.7 in test and disease group. The kidney lactate dehydrogenase, alkaline phosphatase, urinary phosphorus and calcium oxalate level decreased in the test and standard drug groups as compared to disease groups. Microscopy of the urine samples showed reduction in the number of crystals after treatment compared to the urolithic group. Increase in citrate levels in urine in all the treatment groups indicated anti-urolithiatic activity. The test group showed a 69.70% recovery in males and 47.57% recovery in female rats compared to the disease control group. CONCLUSION: Herbmed Plus showed a significant reduction in oxalate synthesizing enzymes suggesting anti-urolithiatic activity and anti-inflammatory and regenerative property in cellular injury caused by crystal deposits.

Safety and efficacy of an herbal formulation in patients with renal calculi - A 28 week, randomized, double-blind, placebo-controlled, parallel group study.

BACKGROUND: Urolithiasis is a growing problem worldwide. Many a times, asymptomatic stones are kept under observation. Many herbal preparations are available for the same, but they lack proper scientific documentation. OBJECTIVE: To study the anti-urolithiatic effect of an herbal preparation, Subap Plus (IP) capsules in patients with asymptomatic renal calculi of size ranging from 4 to 9 mm. MATERIAL AND METHODS: This was a prospective, randomized, double-blind, placebo-controlled clinical trial conducted in a tertiary care hospital in Pune, India. Patients with asymptomatic renal calculi of 4-9 mm size were randomized (1:1, block randomization) to one of the group Subap Plus (treatment group) or placebo (placebo group). The study outcome included change in visual analog scale (VAS), change in the surface area and density of calculi and their expulsion. Statistical analysis was performed using student's t-test and Chi-square test. RESULTS: A total of 120 patients were screened and 84 were enrolled who met the eligibility criteria, of which 65 patients completed the trial (treatment, n = 34; placebo, n = 31). The VAS score significantly decreased in the treatment group (6.9-1.8) than placebo group (7.2-6.8) (p < 0.001). The surface area and density were decreased by 47.58% (p < 0.008) and 43.01% (p < 0.001), respectively, in the treatment group than the placebo group. The expulsion of calculi was significantly higher in the treatment group than placebo group (20.59 vs. 3.23%, p < 0.03). CONCLUSION: Patients treated with herbal formulation showed better expulsion rate and reduction in surface area and density than the placebo group.

Evaluation of a multi-herb supplement for erectile dysfunction: a randomized double-blind, placebo-controlled study.

BACKGROUND: Evidence is lacking for multi-ingredient herbal supplements claiming therapeutic effect in sexual dysfunction in men. We examined the safety and efficacy of VigRX Plus (VXP) - a proprietary polyherbal preparation for improving male sexual function, in a double blind, randomized placebo-controlled, parallel groups, multi-centre study. METHODS: 78 men aged 25-50 years of age; suffering from mild to moderate erectile dysfunction (ED), participated in this study. Subjects were randomized to receive VXP or placebo at a dose of two capsules twice daily for 12 weeks. The international index of erectile function (IIEF) was the primary outcome measure of efficacy. Other efficacy measures were: Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Serum testosterone, Semen analysis, Investigator's Global assessment and Subjects' opinion. RESULTS: In subjects receiving VXP, the IIEF-Erectile Function (EF) scores improved significantly as compared to placebo. After 12 weeks of treatment, the mean (sd) IIEF-EF score at baseline increased from 16.08 (2.87) to 25.08 (4.56) in the VXP group versus 15.86 (3.24) to 16.47 (4.25) in the placebo group (P < 0.0001). Similar results were observed in each of the remaining four domains of the IIEF (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction).There was a significant difference for VXP versus placebo comparison of mean (sd) EDITS scores of patients: 82.31(20.23) vs 36.78(22.53) and partners :(82.75(9.8) vs 18.50(9.44);P < 0.001. Thirty-five out of 39 (90%) subjects from the VXP group and one (3%) from the placebo group wished to continue with the treatment they received. Investigator's global assessment rated VXP therapy as very good to excellent in more than 50% patients and placebo therapy as fair to good in about 25% of patients. Incidence of side effects and subject's rating for tolerability of treatment was similar in both groups. CONCLUSIONS: VigRX Plus was well tolerated and more effective than placebo in improving sexual function in men. TRIAL REGISTRATION: Clinical Trial Registry India, CTRI/2009/091/000099, 31-03-2009.

Management of large (>60 g) prostate gland: PlasmaKinetic Superpulse (bipolar) versus conventional (monopolar) transurethral resection of the prostate.

BACKGROUND AND PURPOSE: Today, urologists around the world are encountering greater numbers of larger prostate glands, probably because of an initial trial of pharmacotherapy. The present study was performed to assess the safety and efficacy of bipolar transurethral resection of large prostate glands using the PlasmaKinetic (PK) Superpulse System. PATIENTS AND METHODS: This single-blind, randomized study included 70 patients with prostate gland >60 g seen on three-dimensional transrectal ultrasonography. Patients were randomized 1:1 using envelopes into either a PK Superpulse transurethral resection of the prostate (TURP) group or conventional TURP group, and underwent the procedure accordingly. Perioperative and postoperative parameters included operative time, blood loss, need for blood transfusion, clinical transurethral resection (TUR) syndrome, and duration of catheterization and hospitalization. Of 70 patients, 67 were followed for a minimum of 9 months, and data were analyzed using SPSS software. RESULTS: Both groups were comparable in terms of preoperative parameters, which included American Urological Association Symptom Score, Qmax, gland size, and postvoid residual. A statistically significant difference between the two groups was found in terms of perioperative blood loss, change in serum sodium, and duration of catheterization. These complications were significantly less in the PK Superpulse group, with an obvious reduction in the duration of hospitalization in that group. CONCLUSION: The PK Superpulse System can be used as safely and effectively in the resection of the large gland (>60 g) as it has been reported to be in the resection of small and medium-sized glands. By using physiologic saline (0.9% NaCl) as irrigation fluid, it eliminates any danger of TUR syndrome and thus eliminates the conventional time limit of resection. PK Superpulse TURP is a promising treatment modality in the management of large prostate glands. It has all the features of gold-standard monopolar TURP, along with added safety and efficacy. It is ready to be included in the urologist's armamentarium.

A prospective, randomized, controlled study to evaluate the efficacy and tolerability of Ayurvedic formulation "varuna and banana stem" in the management of urinary stones.

BACKGROUND: Medical management of urinary calculus disease is a challange for modern science. In the present trial Ayurvedic drug "Herbmed," which is made up of varuna (Crataeva nurvala) and banana stem (Musa paradisiaca) was assessed to see reduction and/or expulsion of urinary calculi and also to assess the role of these drugs to reduce pain during expulsion. MATERIALS AND METHODS: In this prospective randomized, double-blind, placebo control trial, total 77 patients with calculi more than 5 mm were included. All patients were evaluated either by X-ray KUB or USG KUB for 3 months. All patients were divided into two groups: group A included patients with calculi 5-10 mm (n = 31) and group B with calculi > 10 mm (n = 30) with either active treatment or placebo in both the groups. All patients were asked to keep a record of number of pain episodes, while severity of pain was measured on a visual analogue scale (VAS). RESULTS: In group A, there was 33.04% reduction in the size of calculi in the active arm while there was a 5.13% increase in the same group in the placebo arm (p = 0.017). In the other group B, there was an 11.25% reduction in the active arm and a 1.41% reduction in the same group with placebo. In the active arm there was statistically significant lower VAS as compared to the placebo arm in the form of the highest VAS (p = 0.008), average VAS (p = 0.001) and VAS at the first episode of pain (p < 0.0001). CONCLUSIONS: Our preliminary experience suggests that the Ayurvedic formulation "varuna and banana stem" has promise for the management of upper urinary-tract calculi, especially renal calculi. It helps to dissolve renal calculi and facilitate their passage. In addition, it also helps in reduction of pain due to renal/ureteric calculus disease. A larger phase III study with a longer follow-up is required.

PlasmaKinetic Superpulse transurethral resection versus conventional transurethral resection of prostate.

PURPOSE: To compare the efficacy and safety of the PlasmaKinetic (PK) Superpulse system with that of conventional transurethral resection of the prostate (TURP) in terms of restoration of urinary flow and early postoperative course. PATIENTS AND METHODS: One hundred five men older than 45 years with lower-urinary tract symptoms associated with benign prostatic hyperplasia (BPH) were randomized, 51 undergoing standard TURP with glycine as the irrigation fluid and 53 TURP with the PK Superpulse system with normal saline as irrigant. The operative time, intraoperative blood loss, catheter time, change in serum electrolytes (particularly sodium), and uroflowmetry and American Urological Association (AUA) Symptom Scores were compared. RESULTS: The blood loss as well as the catheter time observed in the PK Superpulse arm were significantly less than those in the conventional-TURP arm. The mortality rate was 0 in both the arms. The mean operative time was less in the PK Superpulse arm, although not significantly so. Hyponatremia was statistically insignificant. Significant changes were observed in the AUA Scores in both arms. CONCLUSION: The PK Superpulse system provides faster removal of tissue in a bloodless field with better views and a safer environment of saline irrigation with efficacy comparable to that of conventional TURP. However, further randomized trials with extended follow-up may be needed to better define the role of the PK Superpulse system in treating patients with symptomatic BPH.