Trial In Chinese Patients Research Articles

Pharmacokinetic and safety profiles of mesalazine enema in healthy Chinese subjects: A single- and multiple-dose study.

Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine administered by an enema has not been clarified in Chinese population. We conducted an open-label study to assess the PK and safety profiles of mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 g/100 mL) once daily for 7 consecutive days. Blood and urine samples were collected for assay of mesalazine and N-acetyl mesalazine by liquid chromatography-tandem mass spectrometry. The PK and safety data were summarized using descriptive statistics. The mean (standard deviation) maximum plasma concentration (Cmax), area under plasma drug concentration-time curve from time 0 to the last measurable plasma concentration time point (AUC0-t) and elimination half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) h·ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. The cumulative urinary excretion rate of parent and major metabolite of mesalazine was 27.77%. After the last doe administration, 2.21% of the administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 subjects (36.4%), including oral ulcer, toothache, upper respiratory tract infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and recovered spontaneously without treatment, and were not considered as related to mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy Chinese subjects. These findings support further clinical trials in Chinese patients. Trial registration: This trial was registered to Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn (registration number: ChiCTR2300073148).

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2)

BackgroundHeterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody.MethodsPatients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels.ResultsIn total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: −57.4% [97.5% CI, −69.2 to −45.5] for 150 mg Q2W; −61.9% [−73.4 to −50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension.ConclusionsTafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH.Trial registrationClinicalTrials.gov, NCT04179669.

The clinical efficacy and limitations of dutasteride-regulated abiraterone metabolism in abiraterone-resistant patients: a prospective single-arm clinical trial in Chinese patients.

BackgroundThe steroidal metabolism of abiraterone has been proposed to be involved in abiraterone resistance and limited approaches are available for abiraterone-resistant patients. Dutasteride regulates abiraterone metabolism in patients and might enhance the clinical efficacy of abiraterone. However, the function of dutasteride to overcome abiraterone resistance has not been investigated in clinic. Here we investigated the clinical efficacy and limitations of dutasteride in patients with abiraterone-resistant prostate cancer.MethodsAbiraterone-resistant patients with metastatic castration-resistant prostate cancer (mCRPC) were enrolled in this single-arm, open-label study, patients were treated with dutasteride (0.5 mg/day), abiraterone (1,000 mg/day), and prednisone (5 mg twice daily), prostate-specific antigen (PSA) was tested monthly. The primary objective was PSA response, and the secondary objectives were to assess symptom relief and safety. Kaplan-Meier analysis was used to assess the PSA progression free survival (PSA-PFS) of patients.ResultsTwenty-two patients (median age: 75 years) were enrolled, and 19 patients completed the treatment. After a median treatment of 4.0 months, 7 (37%) patients showed a slight PSA reduction (−2% to −32%), and the median PSA-PFS was 2.0 months (1–7 months). No significant improvement was observed in Eastern Cooperative Oncology Group (ECOG) performance status. Bone pain was relieved in 6 patients after 1 month of treatment, but the improvement was not significant. No grade 3 or grade 4 adverse events were observed.ConclusionsThe combination of dutasteride and abiraterone showed a mild effect in patients with abiraterone-resistant. The small sample size was the limitation of this study.

Hengli® Chinese Botulinum Toxin Type A for Treatment of Patients With Overactive Bladder: A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: To evaluate the efficacy and safety of Hengli® Chinese botulinum toxin type A (BTX-A; 100 U) in Chinese patients with overactive bladder. Methods: This study was a multicenter, randomized, double-blind, placebo-controlled trial in Chinese patients who were inadequately managed with anticholinergic medications. Eligible patients were randomized 2:1 to receive intradetrusor injections of Hengli® BTX-A (n = 144) or placebo (n = 72). The primary endpoint was the change in the number of daily micturition episodes at week 6 from baseline. The secondary efficacy endpoints included the average frequency of urgency and urinary incontinence (UI) episodes per day, urgency score, average micturition volume per day, OABSS, and QoL score. Results: In the Hengli® BTX-A group, there was a significantly greater reduction in the average number of micturition episodes per 24 h compared with the placebo group (3.28 vs. 1.43; p = 0.003). Moreover, there was a significantly greater improvement in the daily number of urgency episodes, micturition volume and OABSS score. An increased post-void residual urine volume, dysuria, and urinary tract infection represented adverse events (AEs) in the Hengli® BTX-A group. Most AEs were mild or moderate in severity. One patient in the BTX-A group initiated clean intermittent catheterization (CIC) during treatment. Conclusion: Hengli® BTX-A treatment was well-tolerated and resulted in significant improvements in OAB symptoms among Chinese patients inadequately managed by anticholinergics. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/clinicaltrials.prosearch.dhtml, Identifier: CTR20131190.

Combination therapy with topical minoxidil and nano-microneedle-assisted fibroblast growth factor for male androgenetic alopecia: a randomized controlled trial in Chinese patients.

Combination therapy with topical minoxidil and nano-microneedle-assisted fibroblast growth factor for male androgenetic alopecia: a randomized controlled trial in Chinese patients.

Effectiveness of PD-1/PD-L1 inhibitors in the treatment of lung cancer: Brightness and challenge

Immune checkpoint inhibitors (ICIs), especially inhibitors of the PD-1/PD-L1 axis, have significantly affected the outcomes of patients with lung cancer. Nivolumab and pembrolizumab have been approved as PD-1 blocking antibodies, whereas atezolizumab, avelumab, and durvalumab are approved as PD-L1 blocking antibodies by the United States Food and Drug Administration. However, which patient may benefit the most and how to identify patients at risk of primary or acquired resistance has not been completely defined. Meanwhile, close attention has been paid to the ongoing international and domestic clinical trials in Chinese patients with lung cancer. This review aimed to provide deep insight into the effectiveness of PD-1/PD-L1 inhibitors in patients with lung cancer, including the current settings for varied disease status, the predictive biomarkers, the resistance to ICIs, and the ongoing clinical trials in Chinese patients.

Anatomic Suitability of Iliac Branched Devices for Chinese Patients with Abdominal-Iliac Aortic Aneurysm

Preserving internal iliac flow is the key to preventing ischemic complications during endovascular aneurysm repair (EVAR). The aim of this study is to determine the morphological features of abdominal aortic aneurysms (AAAs) that have been reported in clinical trials in Chinese patients to identify unique features of iliac branched systems. The data for patients who had common iliac aneurysms suitable for imaging review from 2014 to 2017 at 1 institution in China were reviewed. Three-dimensional workstations were used to measure the centerline diameters and lengths of aortoiliac structures, which were screened for suitability for both Cook iliac branch devices (IBD) and Gore iliac branch endoprosthesis (IBE). A total of 102 lesions of common iliac aneurysms were suitable for imaging review. The anatomic standards for the Gore IBE and Cook IBD were met by 13.7% (14/102) and 9.8% (10/102) of the cases, respectively, and 3 cases were suitable for both devices. The most common cause of not meeting the criteria was the same for both the Cook IBD (78.4%) and Gore IBE (48.03%), which was a limitation of the diameter of the target internal iliac artery. Of the 92 lesions excluded from the Cook IBD trial, 11 (11.9%) were eligible for the Gore IBE trial. Likewise, 7.95% (7/88) of the lesions excluded from the Gore IBE trial would have been eligible for the Cook IBD graft. In a practice that is able to enroll patients in both trials, a total of 20.6% (21/102) of the patients would be eligible for treatment, based on the anatomic criteria. The high incidence of iliac artery involvement in AAAs makes EVAR more complicated. Cook IBD and Gore IBE are only suitable for the treatment of a total of 20.6% Chinese patients based on the anatomic criteria. A limitation in the diameter of the target internal iliac artery is the most common cause of failure to meet the criteria for both devices. Future generations of iliac branch technologies should be designed with diameter accommodations for the hypogastric branch stent to reach a wider group of patients with aortoiliac aneurysmal disease.

The Effect of LM25 and LM50 on Hypoglycemia in Chinese T2DM Patients: Post Hoc Analysis of a Randomized Crossover Trial.

IntroductionTo investigate the safety of insulin lispro Mix 25 and 50 (LM25 and LM50) in hypoglycemia in patients with type 2 diabetes mellitus (T2DM).MethodsThis was a post hoc analysis of a phase IV, randomized, crossover clinical trial in Chinese patients with T2DM switching from premixed human insulin 70/30 (PHI70/30) to LM25 or LM50. Eighty-one subjects received a two-stage crossover protocol of either LM25 or LM50 twice daily for 16 weeks. Habitual diet was taken, and self-monitoring of blood glucose (SMBG) was performed throughout the study period. High-carbohydrate diet (HCD), high-fat diet (HFD) and habitual diet patterns were taken, and 72 h continuous glucose monitoring (CGM) was performed at the last 3 days of each treatment stage.ResultsThe frequencies of nocturnal hypoglycemia in LM50 were lower than those in LM25 under a Chinese habitual diet pattern. The related factors of hypoglycemia in patients with T2DM treated with a LM25 or LM50 regimen were the weight-based daily mean insulin dose and the type of combined oral hypoglycemic agents. Under both HCD and habitual diet patterns, the optimal cut point values of bedtime glucose predicting nocturnal hypoglycemia in LM50 were lower than those in LM25.ConclusionsThe risk of nocturnal hypoglycemia in the LM50 regimen was lower than that in the LM25 regimen under the HCD pattern, and the safety range of bedtime glucose for the LM50 regimen was wider than that of the LM25 regimen in Chinese T2DM patients. Premixed insulin analogs combined with acarbose were more helpful to reduce the incidence of hypoglycemia.Trial Registrationhttp://www.chictr.org.cn #ChiCTR-TTRCC-12002516.

Chinese expert consensus on the use of Zhibitai capsules

The components of Zhibitai capsules are based on classic Chinese traditional medicinal formula, including natural statin, statin homologue, triterpenes and flavonoids. Zhibitai capsules is effective on dyslipidemia by inhibiting cholesterol synthesis and absorption. Several randomized clinical trials in Chinese patients have shown that Zhibitai capsules could reduce low density lipoprotein cholesterol (LDL-C) by 18%-34% and triglycerin (TG) by 30%.Zhibitai capsules had less side effects compared to statins, which interpreted a synergistic effect with Zhibitai capsules. Although no evidence has been proved to use Zhibitai capsules as prophylaxis of cardiovascular diseases, Zhibitai capsules is still an alternative choice of both primary and secondary prophylaxis of cardiovascular diseases.

Su1010 Comparison of Efficacy and Safety of Hyoscine Butylbromide Versus Anisodamine for Acute Gastric or Intestinal Spasm-Like Pain: Results From a Randomized, Double-Blind, Parallel-Group, Multi-Center Phase III Trial in Chinese Patients

Su1010 Comparison of Efficacy and Safety of Hyoscine Butylbromide Versus Anisodamine for Acute Gastric or Intestinal Spasm-Like Pain: Results From a Randomized, Double-Blind, Parallel-Group, Multi-Center Phase III Trial in Chinese Patients

Effects of body mass index or dosage on gastrointestinal disorders associated with extended-release metformin in type 2 diabetes: Sub-analysis of a Phase IV open-label trial in Chinese patients

AimTo determine whether gastrointestinal (GI) tolerability of metformin monotherapy varies according to baseline BMI or at doses >1500mg/day in patients newly diagnosed with type 2 diabetes. MethodsWe performed a sub-analysis of the safety population from a prospective, multicenter, Phase IV open-label study in which 371 Chinese patients with type 2 diabetes received extended-release metformin monotherapy for 16 weeks. The incidence, severity and duration of GI adverse events (AEs) were compared between normal-weight (BMI<25kg/m2, n=155) and overweight/obese (BMI≥25kg/m2, n=216) patients. The primary objective was to determine whether baseline BMI affect the incidence, severity and duration of GI AEs, using Fisher's exact test and Student's t-test. Secondary objectives were to compare these factors according to final metformin dose (≤1500mg/day versus 2000mg/day). ResultsThe proportion of patients who reported ≥1 GI AE did not differ significantly between BMI groups (25.2% of the normal-weight group versus 21.3% of the overweight/obese group; p=0.3840). Patients who reported GI AEs in the two BMI groups experienced similar GI AE severity (p=0.5410), mean duration (p=0.3572) and duration distribution (p=0.1347). There was no significant difference in GI AE severity and duration between metformin dosage groups (≤1500mg/day versus 2000mg/day). ConclusionsNewly-diagnosed Chinese type 2 diabetes patients of normal weight are no more likely than overweight/obese patients to suffer from increased incidence rates, severity or duration of GI AEs when treated with first-line extended-release metformin monotherapy. Doses of 2000mg/day did not increase the severity or duration of GI AEs.

A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Pregabalin for Postherpetic Neuralgia in a Population of Chinese Patients.

Currently, there are limited options for treatment of postherpetic neuralgia (PHN) patients in China. While pregabalin is an effective treatment option for PHN in several countries, there is limited information on its efficacy in Chinese patients. This was an 8-week, double-blind, placebo-controlled trial in Chinese patients with PHN randomized (1:1) to pregabalin 300 mg/day or placebo. Primary efficacy endpoint was change from baseline in mean pain score (Daily Pain Rating Scale; 0 = 'no pain' to 10 = 'worst possible pain'). Secondary efficacy endpoints included change from baseline in overall pain intensity score, by visual analog scale (VAS; 0 = 'no pain' to 100 = 'worst possible pain') and daily sleep interference score (0 = 'pain does not interfere with sleep' to 10 = 'completely interferes'). A total of 220 patients were randomized and received treatment (111 pregabalin and 109 placebo). Improvement in mean pain score with pregabalin was significantly greater than placebo, least squares mean difference (95% CI), -0.71 (-1.08, -0.34); P = 0.0002. Improvements in VAS and sleep interference score at endpoint were significantly greater with pregabalin than placebo, least squares mean difference (95% CI), -8.18 (-11.99, -4.37); P < 0.0001, and -0.54 (-0.93, -0.14); P = 0.0079, respectively. Adverse events were consistent with current product labeling, with dizziness the most commonly reported adverse event (24.3% of pregabalin-treated patients). Pregabalin improved measures of pain and sleep, and is well tolerated in Chinese patients with PHN. These results may inform physicians treating patients with PHN in China.

Intravenous Esomeprazole for Prevention of Peptic Ulcer Rebleeding: A Randomized Trial in Chinese Patients

High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment. This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72h in which 215patients received either high-dose esomeprazole (80mg+8mg/h) or cimetidine (200mg+60mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40mg tablets once daily for 27days. The primary outcome was the rate of clinically significant rebleeding within the first 72h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused. The rate of clinically significant rebleeding within 72h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated. In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China. AstraZeneca. ClinicalTrials.gov identifier, NCT01757275.

Immunotherapy of DC-CIK cells enhances the efficacy of chemotherapy for solid cancer: a meta-analysis of randomized controlled trials in Chinese patients

Professional antigen-presenting dendritic cells (DCs) and cytokine-induced killer (CIK) cells, components of anti-cancer therapy, have shown clinical benefits and potential to overcome chemotherapeutic resistance. To evaluate whether DC-CIK cell-based therapy improves the clinical efficacy of chemotherapy, we reviewed the literature on DC-CIK cells and meta-analyzed randomized controlled trials (RCTs). We searched several databases and selected studies using predefined criteria. RCTs that applied chemotherapy with and without DC-CIK cells separately in two groups were included. Odds ratio (OR) and mean difference (MD) were reported to measure the pooled effect. Twelve reported RCTs (826 patients), which were all performed on Chinese patients, were included. Combination therapy exhibited better data than chemotherapy: 1-year overall survival (OS) (OR=0.22, P<0.01), 2-year OS (OR=0.28, P<0.01), 3-year OS (OR=0.41, P<0.01), 1-year disease-free survival (DFS) (OR=0.16, P<0.05), 3-year DFS (OR=0.32, P<0.01), objective response rate (ORR) (OR=0.54, P<0.01), and disease control rate (DCR) (OR=0.46, P<0.01). Moreover, the levels of CD3(+) T-lymphocytes (MD=-11.65, P<0.05) and CD4(+) T-lymphocytes (MD=-8.18, P<0.01) of the combination group were higher. Immunotherapy of DC-CIK cells may enhance the efficacy of chemotherapy on solid cancer and induces no specific side effect. Further RCTs with no publishing bias should be designed to confirm the immunotherapeutic effects of DC-CIK cells.

Clinical Value of Circulating Tumor Cells in Monitoring Treatment Response in Chinese Patients with Small Cell Lung Cancer

Aim: Although several small-sized retrospective studies have suggested the clinical value of circulating tumor cells (CTCs) in small cell lung cancer (SCLC) patients, its proper application still need further exploration and validation. In a phase III clinical trial in Chinese patients with extensive-stage SCLC, we explored the clinical value of CTCs in predictive and prognostic value. Methods: Blood samples were collected from eighty five patients in this clinical trial, which were randomized to accept etoposide plus lobaplatin (EL) or etoposide plus cisplatin(EP). CTCs from 7.5 ml of blood were analyzed using the CellSearch system at different time points, including prior to the treatment (baseline), after 2 cycles of treatment and disease progression. The relationship between CTC counts and overall survival (OS) was investigated, as well as the clinical significance of CTCs and other validated serum markers. Results: At baseline, ≥5 CTCs/7.5mL blood were 64.7% in the overall patients with 61.7% in the EL arm and 68.4% in the EP arm, however the total rate was decreased to 33.3% after two cycles of treatment with 41.9% in the EL and 23.7% in the EP arms, respectively. The data of CTC counts at disease progression were not mature yet. At baseline as well as after 2 cycles of chemotherapy, the counts of CTC were related with overall survival (OS), the median OS of patients with ≥5 CTCs was significantly shorter than those with 26 months, log rank p 26 months, log rank p<0.0124). In a multivariate analyses, CTCs were demonstrated to be an independent prognostic marker for OS at both baseline (adjusted hazard ratio=0.081, p=0.018) and after 2 cycles of therapy (adjusted HR=0.206; p=0.0249).Moreover statistical significant was found in CA125 after 2 cycles of therapy (adjusted HR=0.208; p=0.0142), but not in CEA and NSE at either time points. Conclusions: This study demonstrated that CTC counts at both baseline and after 2 cycles of chemotherapy are an independent prognostic marker in Chinese patients with extensive-stage SCLC. Compared with conventionally validated serum markers, CTCs may have a superior clinical significant in monitoring therapeutic outcomes of Chinese SCLC patients after chemotherapy. Disclosure: All authors have declared no conflicts of interest.

A cyclic fluctuation model for 24-h ambulatory blood pressure monitoring in Chinese patients with mild to moderate hypertension

The conventional method for analyzing 24-h ambulatory blood pressure monitoring (24-h ABPM) is insufficient to deal with the large amount of data collected. The aim of this study was to develop a novel cyclic fluctuation model for 24-h ABPM in Chinese patients with mild to moderate hypertension. The data were obtained from 4 independent antihypertensive drug clinical trials in Chinese patients with mild to moderate hypertension. The measurements of 24-h ABPM at the end of the placebo run-in period in study 1 were used to develop the cyclic fluctuation model. After evaluated, the structural model was used to analyze the measurements in the other 3 studies. Models were fitted using NONMEM software. The cyclic fluctuation model, which consisted of 2 cosine functions with fixed-effect parameters for rhythm-adjusted 24-h mean blood pressure, amplitude and phase shift, successfully described the blood pressure measurements of study 1. Model robustness was validated by the bootstrap method. The measurements in the other 3 studies were well described by the same structural model. Moreover, the parameters from all the 4 studies were very similar. Visual predictive checks demonstrated that the cyclic fluctuation model could predict the blood pressure fluctuations in the 4 studies. The cyclic fluctuation model for 24-h ABPM deepens our understanding of blood pressure variability, which will be beneficial for drug development and individual therapy in hypertensive patients.

Rationale and design of the ETN-STEP (Early administration of Tirofiban in mid to high risk patients with non-ST elevation acute coronary syndrome referred for percutaneous coronary intervention) project: A multi-center, randomized, controlled clinic trial in Chinese patients

As a member of Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors, Tirofiban had been shown to improve myocardial reperfusion and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI), but the optimal timing of administration of Tirofiban remains unclear. In order to compare the effects of upstream versus downstream administration of Tirofiban in Chinese patients with mid to high risk, non-ST elevation acute coronary syndrome (ACS) referred for PCI, a multi-center, randomized, controlled, prospective study will be conducted. A total of 500 mid to high risk, non-ST-segment elevation myocardial infarction (NSTEMI) ACS patients will be recruited for this study. Patients will be randomized to Tirofiban upstream administration group (initiated 12 h before PCI) and Tirofiban downstream administration group (initiated at cath-lab after angiography). Thrombolysis in myocardial infarction (TIMI) flow grades, TIMI myocardial perfusion grades (TMPG), and Corrected TIMI frame counting (CTFC) before and after PCI, as well as clinical outcomes during the hospital stay, and within 30 days after PCI will be compared between the two groups. This study will provide evidence on the optimal timing for initiating administration of Tirofiban in mid to high NSTEMI ACS subjects undergoing PCI.

Pemetrexed versus docetaxel in second line non-small-cell lung cancer: Results and subsets analyses of a multi-center, randomized, exploratory trial in Chinese patients

BackgroundPemetrexed and docetaxel are established therapies in second line non-small cell lung cancer (NSCLC). Comparative data, concerning the two agents in the designated settings, however, are lacking in Chinese patients who account for the largest lung cancer population in the world. Methods and patientsWe designed and performed a multi-center, randomized, exploratory clinical trial of pemetrexed compared with docetaxel in second line chemotherapy in Chinese NSCLC patients. Eligible patients with histological or cytological diagnosis of stage IIIB or IV NSCLC, who were not suitable for curative therapy and had failed from prior first line chemotherapy regimen for at least 4 weeks, were randomized to receive either pemetrexed 500 mg/m2 intravenously day 1 with vitamin B12, folic acid, and dexamethasone, or docetaxel 75 mg/m2 intravenously day 1 with dexamethasone. Both regimens were implemented once every 21 days for 2 cycles. This study was designed to be a non-inferiority trial that compared tumor response for overall response rate (ORR) between the two drugs as primary endpoint. The secondary endpoints included disease control rate (DCR), Karnofsky performance status (KPS) scores and toxicities. Results260 patients were enrolled and randomly assigned to receive chemotherapy of either pemetrexed (132 patients) or docetaxel (128 patients). 106 patients in pemetrexed arm and 102 patients in docetaxel arm were evaluable for efficacy. The efficacy of pemetrexed was equivalent to that of docetaxel in the second-line treatment for Chinese NSCLC (ORR: pemetrexed vs. docetaxel = 9.4% vs. 4.9, p = 0.285, DCR: pemetrexed vs. docetaxel = 67.2% vs. 69.6%, p = 0.685). And pemetrexed seemed to slightly promote patients' average KPS score when comparing with docetaxel, although the difference was without statistical significance (changes of average KPS scores: pemetrexed vs. docetaxel = 0.28 ± 5.93 vs. -1.67 ± 8.57, p = 0.149). Patients receiving pemetrexed experienced significantly lower incidences of grade 3/4 neutropenia (7.0% vs. 27.6%, p < 0.001) and leucocytopenia (4.7% vs. 22.8%, p < 0.001) than those who received docetaxel. Also, there were lower incidences of alopecia, stomatitis, and neural abnormality for patients receiving pemetrexed than those receiving docetaxel. Incidence of serum glutamic oxaloacetic transaminase elevation, however, was higher in pemetrexed arm than in docetaxel arm (32.3% vs. 14.9%, p = 0.013). In addition, age ≥ 60 patients benefit from pemetrexed with equivalent efficacies yet much lower toxicities compared to docetaxel (DCR: pemetrexed vs. docetaxel = 66.67% vs. 81.58%, p = 0.146; grade 3/4 hematologic toxicities: pemetrexed vs. docetaxel = 17.25% vs. 39.6%, p = 0.016). ConclusionTreatment with pemetrexed resulted in equivalent efficacy outcomes and better safety profiles compared with docetaxel in second-line therapy for advanced NSCLC in Chinese lung cancer population. And age ≥ 60 patients may benefit from second-line single pemetrexed.

The Efficacy and Safety of Cilnidipine on Mild to Moderate Essential Hypertension: A Systematic Review and Meta-analysis of Randomized Controlled Trials in Chinese Patients

The purpose of this study was to evaluate the efficacy and safety of Cilnidipine tablets to treat Chinese patients with mild to moderate essential hypertension, and to examine the ability of Cilnidipine to lower blood pressure without eliciting unfavorable side effects. Medical databases and review articles were screened for randomized controlled trials that reported the effects of and adverse reactions to Cilnidipine and Amlodipine in treating Chinese patients with mild to moderate essential hypertension. The quality of the included studies was critically evaluated. A total of 547 articles were found, from which 11 articles met the inclusion criteria. The heterogeneity test, the efficacy analysis (Q statistic = 4.62, p = 0.91, I(2) = 0%) and safety analysis (Q statistic = 3.73, p = 0.93, I(2) = 0%) showed that Cilnidipine was equally effective and safe compared to Amlodipine. The funnel-plot displayed a symmetrical figure, indicating there was no publication bias, and all articles included described high quality trials. In conclusion, Cilnidipine is a useful agent to treat mild to moderate essential hypertension in China.

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m2), leucovorin (20 mg/m2) bolus, and 5-fluorouracil intravenous infusion (500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.