scholarly journals Randomized Controlled Trial: Neostigmine for Intra-abdominal Hypertension in Acute Pancreatitis

2021 ◽  
Author(s):  
Wenhua He ◽  
Peng Chen ◽  
Yupeng Lei ◽  
Liang Xia ◽  
Pi Liu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Conventional Treatment ◽  
Controlled Trial ◽  
Phase Iii ◽  
Abdominal Pressure ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Abdominal Hypertension ◽  
Significant Difference ◽  
To Receive

Abstract Background: Intra-abdominal hypertension (IAH) in acute pancreatitis (AP) is associated with deterioration in organ function. This trial aimed to assess the efficacy of neostigmine for IAH in patients with AP.Methods: In this single-centre, randomized trial, consenting patients with IAH within 2 weeks of AP onset received conventional treatment for 24 hours. Patients with sustained intra-abdominal pressure (IAP) ≥ 12 mmHg were randomized to receive intramuscular neostigmine (1 mg every 12 hours increased to every 8 hours or every 6 hours, depending on response) or continue conventional treatment for 7 days. The primary outcome was the change of IAP after randomization. Results: A total of 80 patients were recruited to neostigmine (n = 40) or conventional treatment (n = 40). There was no significant difference in baseline parameters. IAP levels were significantly lower in neostigmine group than conventional treatment group at 9 hour (13.8 ± 3.5 vs 15.0 ± 3.1, P = 0.038), 15 hour (13.3 ± 3.4 vs 14.7 ± 3.1, P = 0.015), and 168 hour (12.2 ± 2.7 vs 13.6 ± 3.5, P = 0.045) after randomisation. This effect was more pronounced in patients with baseline IAP ≥ 15 mmHg (all P ≤ 0.038). Stool volume was consistently higher in the neostigmine group during the 7-day period (all P < 0.05). Other secondary outcomes were not significantly different between the two groups.Conclusion: Neostigmine reduced IAP and promoted defecation in patients with AP and IAH. These results warrant a larger, placebo-controlled, double-blind phase III trial.Trial registration: Clinical Trial No: NCT02543658 (registered August /27, 2015). https://clinicaltrials.gov/ct2/show/NCT02543658

A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery

1988 ◽  
Vol 69 (5) ◽  
pp. 687-691 ◽  
Author(s):  
Ross Bullock ◽  
James R. van Dellen ◽  
William Ketelbey ◽  
S. Gustav Reinach
Keyword(s):  
Controlled Trial ◽  
Prophylactic Antibiotics ◽  
Risk Of Infection ◽  
Broad Spectrum Antibiotic ◽  
Wound Sepsis ◽  
Double Blind ◽  
Content Type ◽  
Exact Test ◽  
Significant Difference ◽  
To Receive

✓ In this study, 417 patients undergoing “clean” elective neurosurgical operative procedures were randomized to receive a broad-spectrum antibiotic (piperacillin) or placebo given as three perioperative doses, each 6 hours apart. Randomization was carried out by hospital pharmacists, and the investigators remained blinded until the end of the study. Twenty cases were excluded from analysis because either an unforeseen second operation was performed or antibiotic therapy was initiated within 30 days after surgery to treat infection or the risk of infection. Twelve of the 205 patients treated with placebo developed postoperative wound sepsis, and four of the 192 piperacillin-treated patients developed wound sepsis — a statistically significant difference (p < 0.05, Fisher's exact test). Piperacillin thus appeared to reduce the incidence of neurosurgical wound infection in this study.

Adding oral talactoferrin to first-line NSCLC chemotherapy safely enhanced efficacy in a randomized trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7095-7095 ◽  
Author(s):  
Y. Wang ◽  
D. Raghunadharao ◽  
G. Raman ◽  
D. Doval ◽  
S. Advani ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Strong Association ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind ◽  
Significant Difference ◽  
Anti Cancer ◽  
Evaluable Population ◽  
Cancer Activity

7095 Background: Talactoferrin alfa (TLF) is an oral immunomodulatory protein with a novel mechanism. TLF showed preclinical anti-cancer activity alone and in combination with chemotherapy. In Phase I/II trials, TLF was safe with apparent single-agent anti-cancer activity in non-small cell lung cancer (NSCLC). Methods: 110 chemo-naive patients with advanced or metastatic NSCLC were randomized (1:1) in a multi-center trial to carboplatin/paclitaxel (C/P) therapy plus either TLF or placebo. Starting the day after C/P (C:AUC 5 mg/mL/min; P:175 mg/m2) in chemo-cycles 1, 3 and 5, oral TLF (1.5 g BID) or placebo was administered in 35-day cycles for up to three cycles or until progression. Primary endpoint was Confirmed Response Rate (RR; PR+CR) by CT using RECIST. Secondary endpoints included Progression Free Survival (PFS) and Overall Survival (OS). Results: Baseline patient and disease characteristics were comparable in both groups. All 110 patients were included in the Intent To Treat (ITT) population. 100 patients with at least one CT scan after starting treatment were prospectively defined as the Evaluable population. Adding oral TLF to C/P enhanced efficacy on all endpoints examined including RR, PFS and OS. Confirmed RR in the 100 evaluable patients significantly increased from 29% to 47% (P = 0.05). Confirmed RR in the 110 ITT patients improved from 27% to 42% (P = 0.08). Median PFS in both evaluable and ITT patients improved by 2.8 months (67%). Median OS improved by 31% and 18% in evaluable and ITT patients, respectively. A landmark analysis comparing survival in patients with and without a PR showed a significant difference (P < 0.01), suggesting a strong association between RR and survival. TLF appeared to be very safe and well tolerated with no drug-related SAEs. Fewer AEs were observed in the TLF arm than in the placebo arm, 346 and 432 AEs, respectively (P = 0.0023). The number of Grade 3/4 AEs was also lower in the TLF arm, 60 versus 91 (P = 0.0144). Conclusions: Adding oral TLF to standard C/P chemotherapy in NSCLC was safe and increased efficacy in a randomized, multi-center, double-blind, placebo-controlled trial, with apparent improvements in RR, PFS and OS. Results with TLF compare favorably to other anti-cancer agents. Oral TLF will be further evaluated in a Phase III trial. [Table: see text]

A phase III trial of virulizin plus gemcitabine vs. gemcitabine alone in advanced pancreatic cancer: Results of subgroup analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4116-4116 ◽  
Author(s):  
J. A. Wright ◽  
J. Osterlee ◽  
S. Fekete ◽  
Y. Lee ◽  
A. H. Young
Keyword(s):  
Pancreatic Cancer ◽  
Metastatic Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Double Blind ◽  
Significant Difference ◽  
Ecog Ps ◽  
To Receive

4116 Background: Virulizin (V) is a novel antitumor immune modulator that improves survival in pancreatic cancer patients (pts) as monotherapy. A double-blind, multicenter, randomized, phase III study was conducted to evaluate the survival benefits and safety of V in combination with gemcitabine (G) in pts with advanced pancreatic cancer. Methods: Chemo-naive pts with locally advanced or metastatic pancreatic cancer with ECOG Performance Status (PS) of 0, 1 or 2 were enrolled. Pts were randomized to receive intramuscular injections of either V or placebo (P) 3 times weekly + G (1,000 mg/m2 weekly ×7 with 1 week rest, then weekly ×3 q4w). Randomization was stratified according to ECOG PS (0 or 1, and 2) and extent of disease (locally advanced and metastatic). Pts who showed no clinical benefit or were intolerant to G entered 2nd-line therapy (stage 3), in which pts continued to receive either V or P alone or with 5-FU, or best supportive care. The primary endpoint was survival, defined as time from baseline/treatment day 1 to time of death from any cause. Results: The intent to treat (ITT) population comprised 434 pts, of which 377 were efficacy evaluable (EE). Median overall survival for V + G was 6.3 months for the ITT population (6.8 months for EE pts) and 6 months for P + G for both ITT and EE pts. While differences in survival times were not statistically significant, exploratory analysis showed encouraging results in specific subgroups treated with V + G ( table ). Importantly, a significant difference was found in stage 3 pts who received V in a salvage setting compared to pts who received P. Conclusions: Pancreatic cancer pts with either low ECOG PS or metastatic cancer showed a survival benefit when treated with V + G, which was significant in pts who continued to receive V as a salvage therapy. Further studies in these targeted patient populations are being considered. [Table: see text] No significant financial relationships to disclose.

Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Trifluridine/Tipiracil (TAS-102) Monotherapy in Asian Patients With Previously Treated Metastatic Colorectal Cancer: The TERRA Study

2018 ◽  
Vol 36 (4) ◽  
pp. 350-358 ◽  
Author(s):  
Jianming Xu ◽  
Tae Won Kim ◽  
Lin Shen ◽  
Virote Sriuranpong ◽  
Hongming Pan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Biologic Therapy ◽  
Phase Iii ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Double Blind Placebo ◽  
Asian Patients ◽  
To Receive

Purpose Trifluridine/tipiracil (TAS-102) was effective in patients with metastatic colorectal cancer (mCRC) in a phase II Japanese trial. This regional trial evaluated the efficacy and safety of trifluridine/tipiracil in Asian patients with mCRC with or without exposure to biologic therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase III trial was conducted at 30 sites in China, the Republic of Korea, and Thailand. Patients ≥ 18 years old with histologically or cytologically confirmed adenocarcinoma of the colon or rectum and known KRAS status who were refractory or intolerant to two or more prior chemotherapy regimens were enrolled. Eligible patients were randomly assigned (2:1 ratio; minimization method) to receive trifluridine/tipiracil (twice per day orally; 5 days on and 2 days off for 2 weeks, followed by 14 days off per cycle) or placebo. The primary end point was overall survival (intent-to-treat population). Results Between October 16, 2013, and June 15, 2015, 406 patients were randomly assigned to receive trifluridine/tipiracil (n = 271) or placebo (n = 135). Risk of death was significantly lower in the trifluridine/tipiracil arm than in the placebo arm (hazard ratio for death, 0.79; 95% CI, 0.62 to 0.99; log-rank P = .035). Median overall survival was significantly longer in the trifluridine/tipiracil than in the placebo arm (7.8 months [95% CI, 7.1 to 8.8 months] v 7.1 months [95% CI, 5.9 to 8.2 months], respectively), for a median survival follow-up time of 13.8 months (95% CI, 13.1 to 15.3 months) compared with 13.4 months (95% CI, 11.6 to 17.3 months), respectively. The incidence of serious adverse events was similar between the arms (trifluridine/tipiracil, n = 63 [23.2%]; placebo, n = 32 [23.7%]). No treatment-related deaths were reported. Conclusion Trifluridine/tipiracil has a statistically significant survival benefit compared with placebo in Asian patients with mCRC refractory or intolerant to standard chemotherapies, regardless of exposure to biologic therapy. The safety profile is similar to previous reports.

scholarly journals L-Carnitine Supplementation for the Management of Fatigue in Patients With Cancer: An Eastern Cooperative Oncology Group Phase III, Randomized, Double-Blind, Placebo-Controlled Trial

2012 ◽  
Vol 30 (31) ◽  
pp. 3864-3869 ◽  
Author(s):  
Ricardo A. Cruciani ◽  
Jenny J. Zhang ◽  
Judith Manola ◽  
David Cella ◽  
Bilal Ansari ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Separate Analysis ◽  
Carnitine Supplementation ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Patients With Cancer ◽  
Significant Difference

Purpose L-carnitine, a popular complementary and alternative medicine product, is used by patients with cancer for the treatment of fatigue, the most commonly reported symptom in this patient population. The purpose of this study was to determine the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer. Patients and Methods In this double-blind, placebo-controlled trial, patients with invasive malignancies and fatigue were randomly assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo. The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory (BFI). Results Three hundred seventy-six patients were randomly assigned to treatment with L-carnitine supplementation or placebo. L-carnitine supplementation resulted in significant carnitine plasma level increase by week 4. The primary outcome, fatigue, measured using the BFI, improved in both arms compared with baseline (L-carnitine: −0.96, 95% CI, −1.32 to −0.60; placebo: −1.11, 95% CI −1.44 to −0.78). There were no statistically significant differences between arms (P = .57). Secondary outcomes, including fatigue measured by the Functional Assessment of Chronic Illness Therapy–Fatigue instrument, depression, and pain, did not show significant difference between arms. A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation. Conclusion Four weeks of 2 g of L-carnitine supplementation did not improve fatigue in patients with invasive malignancies and good performance status.

scholarly journals Comparison of azithromycin vs doxycycline prophylaxis in leptospirosis, A randomized double blind placebo-controlled trial

2018 ◽  
Vol 12 (11) ◽  
pp. 991-995
Author(s):  
Ahmad Alikhani ◽  
Ebrahim Salehifar ◽  
Fatemeh Zameni ◽  
Alireza Rafiei ◽  
Jamshid Yazdani-charati ◽  
...  
Keyword(s):  
Paddy Field ◽  
Controlled Trial ◽  
Fisher Exact Test ◽  
Mazandaran Province ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Informed Consent Form ◽  
Significant Difference ◽  
Field Workers ◽  
To Receive

Introduction: Leptospirosis is an important zoonotic disease in paddy field with 29.5% prevalence rate in Mazandaran province and 4% to 52% mortality rate among hospitalized patients. Prevention is an important strategy for the control of this disease. This study aimed to compare the prophylactic effect of azithromycin versus doxycycline against leptospirosis in an endemic area in north of Iran. Methodology: In this randomized double-blind placebo-controlled trial, paddy field workers (n = 187) were randomized to receive azithromycin (500mg weekly), doxycycline (200 mg weekly) or placebo starting one week before exposure to paddy field, during and to four weeks after. Paddy field workers aged 18- 65 years who signed the informed consent form were assessed for signs and symptoms of leptospirosis in addition to serologic evidence of the disease 6th and 12th week. Data were analyzed with SPSS version 13 using Chi-square and Fisher exact test and ANOVA. Results: From June to September 2016, 187 participants were entered the study to receive azithromycin (n = 66), doxycycline (n = 71) or placebo (n = 50). In terms of preventing against clinical leptospirosis, there was not any significant difference between three arms, though there was statistically significant difference of seropositivity after 6 and 12 weeks in comparison to baseline among all three groups (P = 0.029) and between active treatment (eg. azithromycin and doxycycline) groups and placebo group (P = 0.01). Conclusion: Azithromycin like doxycycline decreased seropositivity without significant effect on clinical leptospirosis.

scholarly journals The Effects of Quetiapine on Craving and Withdrawal Symptoms in Methamphetamine Abuse: A Randomized, Double-Blind, Placebo-Controlled Trial

2020 ◽  
Vol 10 (4) ◽  
pp. 29374.1-29374.7
Author(s):  
Najme Sadat Javdan ◽  
◽  
Amir Ghaderi ◽  
Hamid Reza Banafshe ◽  
◽  
...  
Keyword(s):  
Controlled Trial ◽  
Withdrawal Symptoms ◽  
Chi Square ◽  
Double Blind ◽  
Methamphetamine Abuse ◽  
Beneficial Effects ◽  
Amphetamine Withdrawal ◽  
Significant Difference ◽  
Chi Square Test ◽  
To Receive

Background: Patients with Methamphetamine Abuse (MA) are susceptible to many complications like craving, and withdrawal symptoms. These trials were designed to evaluate the effect of quetiapine administration on craving and withdrawal symptoms in MA abuse. Methods: This trial was conducted on 60 people with MA abuse to receive either 100 mg quetiapine (n=30), or placebo (n=30) every day for 2 months. The Desire for Drug Questionnaire (DDQ) and Amphetamine Withdrawal Questionnaire (AWQ) scores were evaluated at baseline and after 2 months’ intervention. For data analysis, t test, and the Chi-square test were applied in SPSS v. 18. Results: Quetiapine significantly decreased DDQ (P=0.002) and AWQ symptoms (P=0.001) compared to the placebo. Furthermore, there was a significant difference among groups in terms of the frequency of negative urine tests (P<0.001). Conclusion: This trial showed that administration of quetiapine supplements for 2 months in individuals with MA abuse had beneficial effects on craving and withdrawal syndrome.

Randomized, double-blind, placebo (PL)-controlled, phase III trial of pimitespib (TAS-116), an oral inhibitor of heat shock protein 90 (HSP90), in patients (pts) with advanced gastrointestinal stromal tumor (GIST) refractory to imatinib (IM), sunitinib (SU) and regorafenib (REG).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11524-11524
Author(s):  
Yoshitaka Honma ◽  
Yukinori Kurokawa ◽  
Akira Sawaki ◽  
Yoichi Naito ◽  
Shiro Iwagami ◽  
...  
Keyword(s):  
Failure Time ◽  
Performance Status ◽  
Phase Iii ◽  
Rank Test ◽  
Clinical Activity ◽  
Double Blind ◽  
Kit Mutation ◽  
Phase Iii Trial ◽  
To Receive ◽  
Advanced Gist

11524 Background: Pimitespib (PIM) is a novel class of orally active selective HSP90 inhibitors. KIT and PDGFRA are clients of HSP90 for their functional stability; therefore, HSP90 is a rational therapeutic target on GIST in pts with acquired resistance, such as secondary mutation in KIT, to approved tyrosine kinase inhibitors. A phase II trial showed clinical activity of PIM in pts with advanced GIST refractory to standard treatments whose medical need remains unmet. This phase III trial evaluated the efficacy and safety of PIM for this unmet clinical need. Methods: Eligible pts had histologically confirmed advanced GIST refractory to IM, SU, and REG, ≥1 measurable lesion, and ECOG performance status 0 or 1. Pts were randomized 2:1 to receive either PIM 160 mg once daily on a 5-days-on/ 2-days-off schedule or PL. Pts eligible for unblinding at the time of progressive disease were allowed to crossover to open-label PIM. The primary endpoint was progression-free survival (PFS) by blinded central radiological review based on modified RECIST 1.1. Secondary endpoints included overall survival (OS), PFS in the pts crossed over to PIM (secondary PFS), and safety. Crossover-adjusted OS was derived using the rank preserving structural failure time (RPSFT) model. Exploratory endpoints included pharmacogenomics (PGx). Results: From Oct 2018 to Apr 2020, 86 pts were randomized to receive either PIM (n = 58) or PL (n = 28). Baseline characteristics were well balanced between the two arms. Median PFS was 2.8 months (mo) (95% CI: 1.6–2.9) for PIM vs. 1.4 mo (95% CI: 0.9–1.8) for PL. The hazard ratio (HR) for PFS was 0.51 (95% CI: 0.30–0.87) ( p = 0.006, stratified log-rank test). Median OS was 13.8 mo (95% CI: 9.2–not reached) for PIM vs. 9.6 mo (95% CI: 5.5–not reached) for PL (HR for OS 0.63; p = 0.081), with 60.7 % of PL pts crossed over to PIM; secondary PFS was 2.7 mo (95% CI: 0.7–4.1). The RPSFT-adjusted median OS of PL was 7.6 mo (adjusted HR for OS 0.42; p = 0.007). Furthermore, the results of PGx analysis suggested that PIM was also effective in pts with secondary KIT mutation detected from blood samples. The most common ( > 5%) grade 3 or higher adverse events (AEs) in PIM/PL were diarrhea (13.8%/0%), anemia (6.9%/10.7%), decreased appetite (6.9%/0%), and tumor hemorrhage (5.2%/0%). AEs leading to PIM/PL study discontinuation were observed in 4/2 pts (6.9%/7.1%), respectively. Conclusions: This randomized trial demonstrated that PIM significantly improved PFS with OS prolongation in pts with advanced GIST refractory to IM, SU, and REG, as a HSP90 inhibitor for the first time. PIM was tolerated and AEs were manageable. With a mechanism of action different from that of standard therapies, PIM has the potential to be a new standard treatment in GIST. Clinical trial information: JapicCTI-184094.

Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma with Fluorouracil, Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie

2008 ◽  
Vol 26 (9) ◽  
pp. 1435-1442 ◽  
Author(s):  
Salah-Eddin Al-Batran ◽  
Joerg Thomas Hartmann ◽  
Stephan Probst ◽  
Harald Schmalenberg ◽  
Stephan Hollerbach ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Significant Difference ◽  
Time To Treatment Failure ◽  
Gastroesophageal Adenocarcinoma ◽  
Reduced Toxicity ◽  
To Receive

Purpose This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer. Patients and Methods Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 (FLO) every 2 weeks or fluorouracil 2,000 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2 weekly, and cisplatin 50 mg/m2 every 2 weeks (FLP). The primary end point was progression-free survival (PFS). Results Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%). FLP was associated with significantly less peripheral neuropathy (22% v 63%). There was a trend toward improved median PFS with FLO versus FLP (5.8 v 3.9 months, respectively; P = .077) and no significant difference in median overall survival (10.7 v 8.8 months, respectively). However, in patients older than 65 years (n = 94), treatment with FLO resulted in significantly superior response rates (41.3% v 16.7%; P = .012), time to treatment failure (5.4 v 2.3 months; P < .001), and PFS (6.0 v 3.1 month; P = .029) and an improved OS (13.9 v 7.2 months) as compared with FLP, respectively. Conclusion FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.

Sign in / Sign up

Export Citation Format

Share Document