99089 Erfurt, Germany

Study to Compare Furmonertinib to Platinum-Based Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations (FURVENT)

A Study of Secukinumab to Evaluate Maintenance of Response in Participants With Non-radiographic Axial Spondyloarthritis Who Achieved Remission

This study will establish whether prolonged chronic dosing with secukinumab is needed in participants with nr-axSpA who have achieved remission. Remission is defined as Ankylosing Spondylitis Disease Activity Score - C-reactive protein (ASDAS-CRP) Inactive Disease (ID) response Inactive Disease (ID) response (ASDAS-CRP < 1.3). The maintenance of remission on continued secukinumab treatment will be evaluated compared to placebo using a randomized withdrawal design. The primary outcome measure for this study is the proportion of participants remaining flare-free at Week 120. Study treatment will be as follows: - Open-label Secukinumab PFS (prefilled syringe) will be labeled as AIN457 150mg/1mL - Double-blind Secukinumab and Placebo PFS will be labeled as AIN457 150mg/1mL/Placebo. Study duration will be up to 128 weeks from Baseline. The treatment duration will be up to 120 weeks with last treatment administration at Week 116. In the Treatment Period 1 participant will attend a site visit approximately 1 month after Baseline and approximately every 12 weeks thereafter. In the Treatment Period 2 participant will attend site visits approximately every 4 weeks.

Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Covid-19

The study has two parts: Part 1 is a multicentre, randomized, double-blind, placebo-controlled phase II clinical study to evaluate the efficacy and safety of Azvudine versus placebo in preventing SARS-CoV-2 infection in household contacts with SARS-CoV-2 infection individuals. The population of part 1 will consist of approximately 450 adults with household contact exposure to individuals with a confirmed SARS-CoV-2 infection.A phase III study will be further conducted if any of the treatment groups reduce SARS-CoV-2 infection rate (Relative risk reduction) > 50% compared with the placebo group. Part 2 is a multicentre, randomized, double-blind, placebo-controlled phase III clinical study. The subject sample size will be calculated based on the results of the Phase II trial. Phase II and phase III studies have the same objectives and primary/secondary end points. The primary endpoint is the proportion of subjects with positive SARS-CoV-2 RT-PCR assay in 7 days. Nasopharyngeal swabs will be collected at D2, D4, D7, D10, and D14 by RT-PCR to confirm SARS-CoV-2 infection.

TESTING -ON Post-Trial ObservatioNal Cohort Study

In the original TESTING study, the median follow-up for full vs reduced dose cohort was 6.1 vs 2.5 years. We learned from the TESTING trial that the composite endpoints (ESKD, 40% reduction in eGFR or death due to kidney disease) tend to start occurring 2-3 years after randomization. At the time of overall study completion, most of the reported endpoints had occurred in participants from the initial, full-dose TESTING cohort. Although we found the effect of corticosteroid is consistent in both doses, longer follow up is required to confirm the beneficial effects on clinically important renal outcomes of the apparently safer reduced reduced-dose cohort, and to confidently compare the effects across doses. As the trial is assessing the effects of a time-limited 6-9-month period of steroids, a post-trial observation cohort study is a critical, cost and resource-efficient method of answering a number of key questions: 1. Is the apparent benefit of glucocorticoid sustained over long term follow-up? 2. Does a lower dose of steroids safely produce similar benefits on long-term kidney outcomes? The primary aim of TESTING-ON is to extend follow up of TESTING study participants and to assess the long-term effects of a 6-9-month course of oral methylprednisolone on end stage kidney disease (ESKD), according to dose (full-dose vs reduced-dose), ethnicity (Chinese vs other) and kidney function (eGFR above and below 60 mL/min/1.73m2). The working hypothesis of TESTING-ON is that a 6-9-month course of oral methylprednisolone will lead to persistent benefits over a long period of time. TESTING-ON is a post-trial observational study of those participants randomized into the TESTING trial who are still alive, haven't reached ESKD and didn't withdraw consent during the trial. Follow-up will continue for up to five years, with further ongoing follow-up should funding allow.

Bioengineered Collagen Implant for Urethral Stricture Repair

Urethral stricture is defined as the abnormal narrowing of the urethral lumen in the area of the corpus spongiosum. A stricture is the result of ischemic spongiofibrosis manifesting as scar tissue in the corpus spongiosum. Long-term consequences are chronic fistulation through the skin, recurrent sepsis, bladder stones, obstructive uropathy, obstructive nephropathy, and finally renal failure. Current available surgical techniques for urethral stricture repair require harvesting of grafts from autologous sites resulting in additional risks of complications at the tissue harvest site and additional pain to the patient. The hypothesis of this study is that the developed bioengineered collagen implant can be used as an alternative biomaterial to buccal mucosa for substitution urethroplasty in urethral stricture patients.

Phase 3 Study to Evaluate Ianalumab on Top of Standard-of-care Therapy in Patients With Systemic Lupus Erythematosus (SIRIUS-SLE 2)

A randomized, double-blind, placebo-controlled multicenter phase 3 study to evaluate efficacy, safety and tolerability of ianalumab on top of standard-of-care therapy in patients with systemic lupus erythematosus (SIRIUS-SLE 2)

Utilization of Compreflex Wraps in Patients With Chronic Venous Insuffciency

In chronic venous insufficiency (CVI), the venous system of the legs is ineffective in performing venous return, and there is venous reflux due to valve failure, physical inactivity and cardiovascular problems, leading to an increase in the pressure in the veins and venous hypertension. Chronic venous insufficiency includes a range of signs and symptoms, including varicose veins, varicose veins, oedema, skin lesions and ulcers. Venous ulcers are wounds that occur due to improper functioning of venous valves secondary to severe chronic venous insufficiency. They are mainly located in the internal lateral zone of the distal third of the leg. Ulcers of venous aetiology make up 80% of all ulcers. They have an incidence of between 15 to 30 per 100'000 personyears. The median healing time for chronic venous ulcers approximates 180 days. These ulcers may produce a foul-smelling discharge, can become infected and cause pain, which, in combination with slow healing and frequent relapses, affects the quality of life of affected patients. The treatment of chronic venous ulcers requires a comprehensive approach for the patient, addressing the etiological factors that determine their evolution, such as venous insufficiency, diet, physical inactivity and postural measures. Local treatment has two components: local ulcer healing and control of venous insufficiency by means of compression therapy. There is evidence that compression therapy promotes the healing process of venous ulcers. However, there is a large number of compression garments available and it is unclear which method of compression is the most effective. Traditionally, multilayered compression banding was the first line management for uncomplicated venous ulcers. This serves to increase venous return and reduce venous hypertension, as well as reduce oedema and improve lymphatic circulation. Despite its importance and widespread use, it has been reported that ca. 50% of patients do not comply with their multilevel bandaging. Reasons for non-compliance are skin irritation, bandage slippage, pain, malodor, inability to maintain hygiene, and discomfort and inability to wear normal footwear. Over recent years, there has been development of several Velcro-based wrap devices for use as alternative compression bandaging for venous ulcer management, using either interlacing or overlapping technique of wrapping. Systematic reviews have been undertaken for Velcro wrap devices, including their use in chronic edema, lipedema, and lymphedema, as well as venous ulceration. These systematic reviews were able to show a reduction in limb volume and more consistent sub-bandage pressure in Velcro wrap devices compared with bandaging. In addition, one of the major advantages that was reported was the relative ease to remove and reapply these devices, which can, therefore, encourage self-care, improve independence and, potentially, quality of life. The Compreflex standard calf and foot (with basic liner) from Sigvaris (St. Gallen, Switzerland) is an easy to use interlacing Velcro wrap device with adjustable compression levels.This Compreflex wrap is intended for patients with mild to moderate lymphedema and venous insufficiency. More than 200'000 products have been sold worldwide since 2016. The product is being used in many European countries (including United Kingdom, Switzerland, Netherland), United States of America, Saudi Arabia, India, Indonesia, Taiwan and Hong Kong, with no product-related safety issues reported. Although the product is not substantially different from other established products that are already available on the market, there are no clinical data published on Compreflex. The present study was therefore designed to confirm the performance of the Compreflex standard calf and foot (with basic liner).

Effectiveness of IV Vitamin C in Reducing Oxidative Stress Associated With Free Flap Surgery

Temporary cessation of blood supply to the flap tissues from clamping of donor vascular pedicle (ischemia) followed by restoration of flap tissue perfusion (reperfusion) after micro-anastomosis are inevitable in any free flap surgery. In combination, the ischemia and reperfusion process during free flap tissue transfers induce a state of increased oxidative stress, which may lead to complications such as flap failure and non-healing wounds at either donor or recipient sites. The negative impacts of which include additional wounds from flap loss, higher costs and increased duration of hospital stay. Previous studies had demonstrated the beneficial effects of ascorbic acid in end-organ protection against ischemia and reperfusion injury. In addition, parenteral ascorbic acid has been shown to be remarkably safe even at high dose in both clinical and nonclinical models. Nonetheless, the data on efficacy of ascorbic acid in free flap survival in human is very limited. The aims of this prospective, multicentre, double-blind, randomized, placebo-controlled pilot study are to measure the extent of oxidative stress in participants undergoing free flap reconstructive surgery before and after administration of parenteral ascorbic acid; and to evaluate its efficacy on modulation of inflammation, flap viability and wound healing. Eligible participants will be randomized to receive 1 gram of parenteral ascorbic acid and 0.9% normal saline (as placebo) 8 hourly for 7 days (from pre-operative day 2 until post-operative day 5). Blood sampling will be performed on day 0 (pre-operative), day 3 (post-operative day 1) and day 5 (post-operative day 3) of intravenous ascorbic acid or placebo infusion for measurement of i) oxidative stress biomarkers, including isoprostane level, gene expression of glutamate-cystein ligase (GCL) and total glutathione level) ii) inflammatory markers, including leucocytes count and gene expression of TNF-α and IL-1. Post-operative outcomes of free flap surgery, up to post-operative 14 days, including flap viability, wound healing at both donor and recipient sites and duration of ICU and hospital stay will be evaluated. The investigators estimate that a total sample of 28 participants (14 on each arm) will be necessary for 80% power to detect a 33% oxidative stress reduction with medium effect size (0.5) at 5% level of significance (α) between treatment (intravenous ascorbic acid) and placebo group (0.9% normal saline). A total of 34 participants are required to account for 20% of dropouts. Primary analysis of this study utilizes an intention-to-treat approach and includes all randomized participants undergoing elective free flap reconstructive surgery. The mean difference between the baseline (pre-operative) and post-operative oxidative stress and inflammatory levels will be analyzed and compared between the intravenous ascorbic acid and placebo group using analysis of variance (ANOVA) for all normally distributed dataset whilst the non-parametric Kruskal-Wallis test is used, if otherwise. The effect size of such difference will be determined and compared. Subsequently, correlation between reduction of oxidative stress and post-operative flap outcomes in the intravenous ascorbic acid group will be evaluated. The secondary outcomes such as flap viability (percentage of flap necrosis), wound healing at both recipient and donor sites (percentage of wound dehiscence and percentage of skin graft failure to take/loss), duration of hospital and ICU stay and wound infection rate will be presented as mean with standard deviation (SD) or median with interquartile range (IQR) based on their normality distribution and are compared with Student's t-test or Mann-Whitney U test.

Difference of Basal Insulin Titration Method in Reducing HbA1c Among Type 2 Diabetes Mellitus (T2DM) Patients.

Hypothesis Daily basal insulin titration reduces HbA1c more significantly compared with 3 daily basal insulin titration among T2DM patients. Aims Primary Aim : To evaluate the difference of daily basal insulin titration method and 3-daily basal insulin titration method in reducing HbA1c among T2DM patients Secondary Aim : To evaluate the percentage of T2DM patients achieving fasting blood sugar within 4.4-7mmol/L and/or HbA1c below 7% within the study period, frequency of hypoglycemia, total daily basal insulin dosage needed to achieve fasting capillary blood glucose 4.4-7mmol/L, duration taken to achieve optimal fasting capillary blood glucose 4.4-7mmol/L, weight changes and satisfaction to the titration therapy between the daily basal insulin and 3-daily basal insulin titration method. Background and Clinical Significance Background Diabetes Mellitus is a worrying non communicable disease both locally and globally. Malaysia Nasional Heath and Morbidity Survey 2019 (NHMS 2019) reported the prevalence of diabetes mellitus was 18.3%, an increase from year 2011 (11.2%) and year 2015 (13.4%). With the prevalence of nearing 1 in 5 adult Malaysian suffering from diabetes mellitus, a good control of the disease is the ultimate way to prevent diabetes related complications from occurring, namely stroke, heart attack and kidney failure. Insulin is one of the most widely used injectable diabetic medications that is suitable to be incorporated with a wide range of antidiabetic medications such as oral antidiabetic drugs (OAD) and GLP-1 receptor agonists (GLP-1 RA). Insulin therapy should be considered in T2DM patients that have inadequate glycemic control (HbA1c >7.5% with Fasting capillary blood glucose (CBG) >8 mmol/L) on optimal OADs and it should also be used as an initial therapy in newly diagnosed T2DM patients who are symptomatic (osmotic symptoms), Hba1c >10% or fasting plasma glucose >13mmol/L. The enormous diabetic patients in Malaysia, largely managed in governmental clinic/ hospital setting pose the technical difficulty for clinicians to review them at regular basis. An average duration of a face-to-face consultation at an outpatient setting is scheduled at 3 monthly to 6 monthly intervals. This makes it a technical difficulty for insulin users to titrate their medications if they are purely managed by clinicians. Patient-lead basal insulin titration has been proven to be more effective than clinician-driven insulin titration to achieve the HbA1c target. It is also proven that outpatient patient-lead basal insulin titration is easy to achieve targeted HbA1c compared with clinician-driven OADs titration. Local Malaysia CPG guideline suggested weekly basal insulin titration to achieve glycemic target.2 Where else American Diabetes Association 2019 advocate adjustment of basal insulin by 2-4 units once or twice a week to achieve the desired fasting blood sugar level.6 In the context of Canadian 2018 Diabetes CPG, they suggest 1 unit daily adjustment of basal insulin to achieve targeted fasting blood sugar level.7 Various studies using different patient-lead basal insulin titration regimen ranging from 1 unit per day to 2-3 units every 3 days have proven to be efficacious and safe in achieving HbA1c target among the T2DM patients. Clinical Significance This study hopes to achieve a best outpatient patient-lead basal insulin titration whether daily 1 unit titration or 3 daily 2 units titration is better in achieving the targeted HbA1c. This will also enable us to evaluate which titration regimen is safer and easier to adhere among T2DM patients who require basal insulin commencement. Study Design This study is designed as a parallel group randomized controlled trial with 12 weeks of intervention and follow up. The total duration of participation is 12 weeks. Participants Adult T2DM patients Inclusion Criteria 1. Adults aged 18 years and above 2. HbA1c >7.5% and Fasting blood sugar > 8mmol/L 3. Newly diagnosed T2DM with osmotic symptoms or HbA1c >10% or FPG >13mmol/L 4. Insulin naïve patients 5. Patients planned for insulin initiation 6. Ability to give informed consent 7. Ability to perform self-monitoring blood glucose Exclusion Criteria 1. Diabetes other than type 2 diabetes mellitus 2. Diabetes in pregnancy 3. Diabetes with chronic kidney disease stage 3,4 and 5 (eGFR <60ml/min/1.73m2) 4. Patient with history of severe hypoglycemia 5. Active proliferative diabetic retinopathy 6. Any medical condition that may influence HbA1c measurements (e.g., thalassemia, sickle cell anemia) 7. Treatment with systemic corticosteroid Intervention Basal insulin daily titration arm Participants in this intervention arm will be started with basal insulin of 10 units or 0.2 unit/kg (whichever lower) at pre-bed time. They will then check their morning fasting CBG the following day. If they have no hypoglycemia symptoms or documented hypoglycemic CBG (<3.9mmol/L), and their fasting CBG is more than 7mmol/L, they will then self-titrate their basal insulin by 1 unit (ie 10+1) the following night. This same process is going to be repeated until their fasting CBG achieve 7mmol/L or lower. Then, they will continue and maintain on the desired basal insulin dosage till their appointment. The maximum basal insulin that is allowed to be titrated by the participants is up to 0.5unit/kg. Participants are required to document down their CBG and any hypoglycemia symptoms in a simple table method provided to them. At any instance if their morning fasting CBG is higher than 14mmol/L, phone consultation can be made to the investigator and further titration of medication or further plans will be instructed by the investigator. If their overnight CBG is <3.9mmol/L, participants are instructed to reduce their basal insulin by 10-20%. Participants are able to contact the investigator if they experience hypoglycemic symptoms if they are unsure of the subsequent steps. A clear hypoglycemia action plan will be provided to all participants. Basal insulin 3-daily titration arm Participants in this intervention arm will be started with basal insulin of 10 units or 0.2 unit/kg (whichever lower) at pre-bed time. They will then check their morning fasting CBG the following 3 days. If they have no hypoglycemia symptoms or documented hypoglycemic CBG (<3.9mmol/L), and their fasting CBG is more than 7mmol/L (for 2 out of 3 days), they will then self-titrate their basal insulin by 2 units (ie 10+2) on the 3rd night. This same process is going to be repeated until their fasting CBG achieved 7mmol/L or lower. Then, they will continue and maintain on the desired basal insulin dosage till their appointment. The maximum basal insulin that is allowed to be titrated by the participants is up to 0.5unit/kg. Participants are required to document down their CBG and any hypoglycemia symptoms in a simple table method provided to them. At any instance if their morning CBG is higher than 14mmol/L, phone consultation can be made to the investigator and further titration of medication or further plans will be instructed by the investigator. If their overnight CBG is <3.9mmol/L, participants are instructed to reduce their basal insulin by 10-20%. Participants are able to contact the investigator if they experience hypoglycemic symptoms if they are unsure of the subsequent steps. A clear hypoglycemia action plan will be provided to all participants. Hypoglycemia, Classification and Action Plans Hypoglycemia is defined by either - CBG <3.9mmol/L - Presence of autonomic or neuroglycopenic symptoms - Reversed by carbohydrate (CHO) intake Classification Level 1 - CBG 3-3.9mmol/L Level 2 - CBG <3mmol/L Level 3 - Hypoglycemia requires assistance from another person for recovery Action Plans Level 1 & 2 - consume 15g of CHO (eg: 1 tablespoon of honey, 150-200ml of fruit juice or soft drink or 3 teaspoons of table sugar dissolve in water) - repeat CBG within 15 minutes - if CBG is still < 3.9mmol/L, consume another 15g of CHO (to be repeated until CBG>3.9mmol/L) - if CBG is >3.9mmol/L, to reduce basal insulin by 10-20% Level 3 - if patient is still conscious, follow steps for Level 1 & 2 - if patient is unconscious, to rush to emergency department Outcomes measures 1. Primary Outcome a. To compare the HbA1c reduction of the daily basal insulin titration arm with the 3-daily basal insulin titration arm 2. Secondary Outcome 1. To compare the percentage of patient achieving fasting blood glucose within 4.4-7mmol/L and/or HbA1c below 7% between the daily basal insulin titration arm with the 3-daily basal insulin titration arm within the study period 2. To compare the frequency of hypoglycemia between the daily basal insulin titration arm with the 3- daily basal insulin titration arm 3. To compare the total basal insulin dosage required to achieve normal fasting CBG 4.4-7.0mmol/L between the daily basal insulin titration arm with the 3-daily basal insulin titration arm 4. To compare the duration taken to achieve normal fasting CBG 4.4-7.0mmol/L between the daily basal insulin titration arm with the 3-daily basal insulin titration arm 5. To compare the satisfaction to the titration method between the daily basal insulin titration arm with the 3-daily basal insulin titration arm 6. To compare with weight changed between the daily basal insulin titration arm with the 3-daily basal insulin titration arm Study Protocol Week 0 Upon enrolment, demographic data will be collected. Fasting plasma glucose and HbA1c records will be collected. Both intervention groups will receive glucometer devices and strips; they will be advised to record their CBG readings and the hypoglycemic symptoms on the tables given. Week 4 and Week 8 Teleconsultation will be made by the investigator to ensure the optimal dosages of basal insulins are commenced. Any doubts and difficulties along the titration will be answered during the teleconsultations. Week 12 Face-to-face consultation will be made. Blood taking will be collected for HbA1c and FPG during the visit. Handling of the recorded glucose-reading table will be done. A simple questionnaire regarding satisfaction of the titration regimen will be carried out. Participants will be discharged back to their previous physician care. Data analysis and interpretation Patients' demographic and clinical characteristics at baseline will be compared between the intervention arm 1 and intervention arm 2. Continuous data will be summarized as means (±standard deviation) and categorical data will be summarized as frequencies (%). Depending on the normality distribution, continuous outcomes will be compared between those in the arm 1 and arm 2 groups using a two-sample t-test or Mann-Whitney U test while categorical outcomes will be compared using the Fisher's exact test or Chi-square test. The treatment effect will be expressed as relative risk (95% CI). A p value of <0.05 will be considered significant. 5. Sample Size Calculation Anticipating 10% dropout from each group, A total of (32+32) X 1.1 = 70 subjects will be recruited in the study Mean HbA1c for 3 daily basal insulin adjustment is 7.8% [AT.LANTUS] Mean HbA1c for daily basal insulin adjustment is 6.96% [Canadian INSIGHT]