Efficacy of Stannous Ions on Enamel Demineralization under Normal and Hyposalivatory Conditions: A Controlled Randomized in situ Pilot Trial

The study aim was to investigate the effect of antierosive agents on enamel under normal and hyposalivatory conditions. This double-blind crossover in situ pilot study evaluated 4 toothpastes: placebo (0 ppm F), sodium fluoride (NaF, 1,450 ppm), stannous/sodium fluoride (SnF/NaF, 1,450 ppm F-, 1,090 ppm Sn2+), and sodium fluoride, stannous chloride and chitosan (NaF/Sn/Ch, 1,450 ppm F-, 3,500 ppm Sn2+, 0.5% Ch). Twenty participants were assigned to 2 groups (n = 10 each): normal and low salivary flow. Participants wore palatal appliances holding 4 bovine enamel specimens previously eroded in vitro (D1) for 20 min prior to an in situ phase after which they were eroded again (D2). Surface microhardness was determined at baseline (BL), after D1, in situ phase and D2 to assess hardness loss (%SMH), residual hardness loss (%RHL) and erosion resistance (%RER). Additional specimens were evaluated by scanning electron microscopy after the in situ phase. ANOVA and a factorial analysis for between-subject effects were performed. Sn-based toothpastes showed the best effects (p < 0.05). Under normal flow, SnF/NaF showed higher efficacy, with a significant difference compared to NaF/Sn/Ch, NaF, and placebo (p < 0.05). Under low flow, SnF/NaF and NaF/Sn/Ch were comparable (p > 0.05); NaF and placebo were statistically similar. Comparing salivary conditions, there were significant differences for SnF/NaF for %SMH after the in situ phase (%SMHtotal)), %RHL and for all toothpastes in case of %RER. Factorial analysis revealed interactions between toothpaste and saliva flow for %SMHtotal and %RHL. Salivary flow can influence the efficacy of the antierosive toothpastes; however, Sn2+ preparations show even under low salivary flow conditions the highest efficacy in the prevention of enamel erosion.

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A randomised pilot trial of the anti-von Willebrand factor aptamer ARC1779 in patients with type 2b von Willebrand disease

Thrombosis and Haemostasis ◽

10.1160/th10-01-0027 ◽

2010 ◽

Vol 104 (09) ◽

pp. 563-570 ◽

Cited By ~ 44

Author(s):

Petra Paulinska ◽

Petra Jilma-Stohlawetz ◽

James Gilbert ◽

Renta Hutabarat ◽

Paul Knöbl ◽

...

Keyword(s):

Pilot Trial ◽

Coagulation Factor ◽

Von Willebrand Disease ◽

Double Blind ◽

Clinical Trial Registration ◽

Maximal Increase ◽

Double Blind Design ◽

Von Willebrand

SummaryDesmopressin aggravates thrombocytopenia in type 2B von Willebrand disease (VWF type 2B) by release of large and hyper-adhesive von Wille-brand Factor (VWF) multimers. This pilot study investigated whether the anti-VWF aptamer ARC1779 can prevent desmopressin-induced thrombocytopenia and interferes with the excessive VWF turnover in patients with VWF type 2B. Concentration effect curves of ARC1779 were established for five patients in vitro and two patients with VWF type 2B were treated by infusion of ARC1779, desmopressin, or their combination in a randomised, controlled, double-blind design. ARC1779 concentrations in the range of 1–3 μg/ml blocked free A1 domain binding sites by 90% in vitro. In vivo, desmopressin alone induced a profound (-90%) drop in platelet counts in one of the patients. ARC1779 (4–5 μg/ml) completely inhibited VWF A1 domains and prevented this desmopress-in-induced platelet drop. Desmopressin alone increased VWF antigen two- to three-fold, accompanied by concordant changes in VWF Ristocetin cofactor activity (RCo) and coagulation factor VIII activity. ARC1779 substantially enhanced the desmopressin-induced maximal increase in these parameters, and improved multimer patterns. No treatment related adverse events were observed and no bleeding occurred despite marked thrombocytopenia. These data provide first proof of concept in humans and evidence that ARC1779 is a potent inhibitor of VWF. ARC1779 prevented the rapid consumption of VWF multimers together with agglutinated platelets that occurred in response to desmopressin challenge in patients with VWD type 2B.Clinical Trial registration number: NCT00632242.

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Therapeutical aspect of trichomoniasis

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0304156v ◽

2003 ◽

Vol 131 (3-4) ◽

pp. 156-162 ◽

Cited By ~ 1

Author(s):

Jelica Vukicevic ◽

Jasmina Jankicevic

Keyword(s):

Trichomonas Vaginalis ◽

Communicable Disease ◽

Repeated Administration ◽

Transmitted Infection ◽

Microbiological Test ◽

Clinical Forms ◽

Short Period ◽

Significant Difference

Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole) according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center) [19]. The resistance of Trichomonas vaginalis (TV) strains to metronidazole (MND) was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001) 612 patients (244 females and 368 males) suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects). Trichomonas infection was found in 90 (36.88 %) out of 244 tested females and in 126 (32.34 %) of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases). The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05). The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three phases proceeding in succession, in so far TV had not been eliminated by previous one. The number of cured patients, according to therapeutical phases, was shown in Table 4. Three patients (1.39 %, 2 males and 1 female) were not cured in spite of all three completed phases of therapeutical protocol. In all three cases, TV was eliminated by MND application in dose of 3 g/daily, during two days. The failure of minute MND treatment was analyzed in relation to clinical forms of the infection (manifested or asymptomatic), as well as in relation to types of infection (single- or associated infection). The incidence of refractory trichomoniasis treated by a single metronidazole dose of 2 g was significantly higher in the group of patients with polyinfection (c2=18.270 p<0.01). There was no significant difference of resistance to a single MND dose between the groups with manifested and asymptomatic trichomoniasis (c2=0.321; p<0.01). The prevalence of TV in vaginal and urethral smears indicates the significant incidence of trichomoniasis in STD. TV was more frequently isolated in patients with clinically manifested infection. TV susceptibility to MND was tested in vitro in aerobic and anaerobic conditions. The resistance of strains under in vitro conditions did not correlate with refractory feature of trichomoniasis to MND application [7 17, 18]. The success of trichomoniasis treatment depends upon multiple factors, including: a) TV susceptibility to drug, b) intravaginal redox potential, c) drug concentration in situ, d) associated microorganisms that may modify the amount of the drug available in situ [7, 18, 21]. The results of our investigation argue for the latter item, verifying that TV resistance to MND is higher in patients with polyinfection in relation to those with monoinfection (significant difference, c2=18.270; p<0.01). Repeated administration of low metronidazole doses may prolong the therapy of trichomonas infections, while application of high doses (over 3 g/day) may result in undesired complications. Given the well-known fact that repeated sublethal doses induce the resistance, would it be more beneficial to begin with slightly higher metronidazole dose (3 g/day) during short period of time (3-5 days)? This will be the subject of our further investigation.

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Effect of 10% and 15% Carbamide Peroxide on Fracture Toughness of Human Dentin In Situ

Operative Dentistry ◽

10.2341/12-127-c ◽

2013 ◽

Vol 38 (2) ◽

pp. 142-150 ◽

Cited By ~ 3

Author(s):

LE Tam ◽

P Bahrami ◽

O Oguienko ◽

H Limeback

Keyword(s):

Fracture Toughness ◽

Placebo Group ◽

Color Change ◽

Carbamide Peroxide ◽

Tooth Sensitivity ◽

Custom Made ◽

Dental Hard Tissues ◽

Significant Difference

SUMMARY Purpose Although damage to the structural integrity of the tooth is not usually considered a significant problem associated with tooth bleaching, there have been some reported negative effects of bleaching on dental hard tissues in vitro. More studies are needed to determine whether the observed in vitro effects have practical clinical implications regarding tooth structural durability. Objectives This in situ study evaluated the effect of 10% and 15% carbamide peroxide (CP) dental bleach, applied using conventional whitening trays by participants at home, on the fracture toughness of dentin. Methods Ninety-one adult volunteers were recruited (n ≈ 30/group). Compact fracture toughness specimens (approximately 4.5 × 4.6 × 1.7 mm) were prepared from the coronal dentin of recently extracted human molars and gamma-radiated. One specimen was fitted into a prepared slot, adjacent to a maxillary premolar, within a custom-made bleaching tray that was made for each adult participant. The participants were instructed to wear the tray containing the dentin specimen with placebo, 10% CP, or 15% CP treatment gel overnight for 14 nights and to store it in artificial saliva when not in use. Pre-bleach and post-bleach tooth color and tooth sensitivity were also evaluated using ranked shade tab values and visual analogue scales (VASs), respectively. Within 24–48 hours after the last bleach session, the dentin specimens were tested for fracture toughness using tensile loading at 10 mm/min. Analysis of variance, Kruskal-Wallis, χ2, Tukey's, and Mann-Whitney U tests were used for statistical analysis. The level of significance was set at p<0.05 for all tests, except for the Mann-Whitney U tests, which used a Bonferroni correction for post hoc analyses of the nonparametric data (p<0.017). Results The placebo, 10% CP, and 15% CP groups contained 30, 31, and 30 participants, respectively. Mean fracture toughness (+ standard deviation) for the placebo, 10% CP, and 15% CP groups were 2.3 ± 0.9, 2.2 ± 0.7, and 2.0 ± 0.5 MPa*m1/2 respectively. There were no significant differences in mean fracture toughness results among the groups (p=0.241). The tooth sensitivity VAS scores indicated a significantly greater incidence (p=0.000) and degree of tooth sensitivity (p=0.049 for VAS change and p=0.003 for max VAS) in the bleach groups than in the placebo group. The color change results showed generally greater color change in the bleach groups than in the placebo group (p=0.008 for shade guide determination and p=0.000 for colorimeter determination). Conclusions There were no significant differences in in situ dentin fracture toughness results among the groups. The results of this study provide some reassurance that dentin is not overtly weakened by the bleaching protocol used in this study. However, the lack of a statistically significant difference cannot be used to state that there is no effect of bleach on dentin fracture toughness.

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Evaluation of the efficacy of an appeasing pheromone diffuser product vs placebo for management of feline aggression in multi-cat households: a pilot study

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x18774437 ◽

2018 ◽

Vol 21 (4) ◽

pp. 293-305 ◽

Cited By ~ 8

Author(s):

Theresa L DePorter ◽

David L Bledsoe ◽

Alexandra Beck ◽

Elodie Ollivier

Keyword(s):

Treatment Group ◽

Positive Reinforcement ◽

Pilot Trial ◽

Time Factor ◽

Educational Training ◽

Double Blind ◽

Aggression Score ◽

Significant Difference ◽

Full Analysis ◽

Promising Treatment

Objectives Aggression and social tension among housemate cats is common and puts cats at risk of injury or relinquishment. The aim of this study was to evaluate the effectiveness of a new pheromone product in reducing aggression between housemate cats. Methods A new pheromone product (Feliway Friends) containing a proprietary cat-appeasing pheromone was evaluated for efficacy in reducing aggression between housemate cats via a randomized, double-blind, placebo-controlled pilot trial of 45 multi-cat households (pheromone [n = 20], placebo [n = 25]) reporting aggression for at least 2 weeks. Each household had 2–5 cats. Participants attended an educational training meeting on day (D) –7 and the veterinary behaviorist described behaviors to be monitored for 7 weeks using the Oakland Feline Social Interaction Scale (OFSIS), which assessed the frequency and intensity of 12 representative aggressive interactions. Participants were also provided with instructions for handling aggressive events, including classical conditioning, redirection by positive reinforcement and not punishing or startling the cat for aggressive displays. Punishment techniques were strongly discouraged. Plug-in diffusers with the pheromone product or placebo were utilized from D0–D28. Participants completed a daily diary of aggressive events and weekly OFSIS assessments through to D42. Results Evolution of the OFSIS–Aggression score according to treatment group in the full analysis set population revealed a significant effect on time and treatment group. The OFSIS–Aggression score decreased over time from D0–D28 in both groups (time factor P = 0.0001) with a significant difference in favor of the verum P = 0.06); similar results were found considering the D0–D42 period (time factor P = 0.0001 [D0] and P = 0.04 [D42]). Conclusions and relevance The OFSIS provided a quantifiable measure of the frequency and intensity of 12 intercat interactions reflecting conflict between cats. The cat-appeasing pheromone is a promising treatment for the management of aggression between housemate cats in multi-cat households.

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Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage

BMC Neurology ◽

10.1186/s12883-020-01908-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Peter Y. M. Woo ◽

Joanna W. K. Ho ◽

Natalie M. W. Ko ◽

Ronald P. T. Li ◽

Leo Jian ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Adverse Effects ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Pilot Trial ◽

Delayed Cerebral Ischemia ◽

Trial Registration ◽

Study Group ◽

Double Blind ◽

Link Type ◽

Significant Difference

Asbtract Background There are limited neuroprotective treatment options for patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrolysin, a brain-specific proposed pleiotropic neuroprotective agent, has been suggested to improve global functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of administering Cerebrolysin for SAH patients. Methods This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. Fifty patients received either daily Cerebrolysin (30 ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Scale (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the modified Ranking Scale (mRS), the Montreal Cognitive Assessment (MOCA) score, occurrence of adverse effects and the occurrence of delayed cerebral ischemia (DCI). Results No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43–5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79–15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28–2.59). Conclusions Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients. Clinical trial registration Name of Registry: ClinicalTrials.gov Trial Registration Number: NCT01787123. Date of Registration: 8th February 2013.

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Materials Sealing Preventing Biofilm Formation in Implant/Abutment Joints: Which Is the Most Effective? A Systematic Review and Meta-Analysis

Journal of Oral Implantology ◽

10.1563/aaid-joi-d-19-00121 ◽

2020 ◽

Vol 46 (2) ◽

pp. 163-171

Author(s):

Cecília Alves de Sousa ◽

Maria Beatriz Bello Taborda ◽

Gustavo Antônio Correa Momesso ◽

Eduardo Passos Rocha ◽

Paulo Henrique dos Santos ◽

...

Keyword(s):

Systematic Review ◽

Biofilm Formation ◽

Meta Analysis ◽

Significance Level ◽

Gutta Percha ◽

Significant Difference ◽

Physical Barriers ◽

External Connection

The purpose of this systematic review was to evaluate the literature available for materials exhibiting the best efficacy in preventing biofilm formation in the interior of implants. We searched PubMed/MEDLINE, Scopus, and Cochrane databases. This review is registered with the PROSPERO database and followed the suitability of the PRISMA protocol. The initial search resulted in 326 articles from the databases. After they were read, 8 articles remained, and the inclusion and exclusion criteria were applied. Six of these 8 articles were classified as in vitro and 2 were classified as in situ. The regions of the implants evaluated ranged from the interface of the pieces to the occlusal upper access of the abutment. The implant connections evaluated the Morse taper, external connection, and internal connection. Meta-analysis of the quantitative data was performed at a significance level of .05. Cotton exhibited poor control of infiltration, even in combination with other materials. Isolated gutta-percha (GP) and polytetrafluoroethylene (PTFE) tape with composite resin (CR) or GP performed better as physical barriers. The best results for chemical barriers were observed by the application of 1% chlorhexidine gluconate (CG) gel, thymol varnish, and the deposition of Ag films onto the surface. The applied meta-analysis did not show a significant difference in comparison between the different types of implant connections (P > .05). The application of CG and thymol varnish antimicrobials was effective in preventing biofilm formation and easy clinical execution; these could be used in combination with CR, GP, and PTFE.

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Comparative efficacy of a hydroxyapatite and a fluoride toothpaste for prevention and remineralization of dental caries in children

BDJ Open ◽

10.1038/s41405-019-0026-8 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 12

Author(s):

Bennett T. Amaechi ◽

Parveez Ahamed AbdulAzees ◽

Dina Ossama Alshareif ◽

Marina Adel Shehata ◽

Patrícia Paula de Carvalho Sampaio Lima ◽

...

Keyword(s):

Pairwise Comparison ◽

Oral Appliance ◽

Comparable Efficacy ◽

Double Blind ◽

Fluoride Toothpaste ◽

Initial Caries ◽

Significant Difference ◽

Post Test ◽

Amine Fluoride

Abstract Objective This in situ study compared the effectiveness of two toothpastes containing hydroxyapatite or 500 ppm fluoride in promoting remineralization and inhibiting caries development. Materials and methods Two enamel blocks (human primary teeth), one sound and one with artificially-produced caries lesion, were exposed to toothpaste containing either 10% hydroxyapatite or 500 ppm F− (amine fluoride) via intra-oral appliance worn by 30 adults in two-arm double blind randomized crossover study lasting 14 days per arm (ClinicalTrials.gov: NCT03681340). Baseline and post-test mineral loss and lesion depth (LD) were quantified using microradiography. One-sided t-test of one group mean was used for intragroup comparison (baseline vs. post-test), while two-sided t-test of two independent means was used to compare the two toothpaste groups. Results Pairwise comparison (baseline vs. test) indicated significant (p < 0.0001) remineralization and LD reduction by either toothpaste; however, when compared against each other, there was no statistically significant difference in remineralization or LD reduction between the two toothpastes. No demineralization could be observed in sound enamel blocks exposed to either toothpaste. While F− induced lesion surface lamination, HAP produced a more homogenous lesion remineralization. Conclusions 10% hydroxyapatite achieved comparable efficacy with 500 ppm F− in remineralizing initial caries and preventing demineralization. Thus the HAP toothpaste is confirmed to be equal to the fluoride toothpaste in this study.

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Efficacy and Safety of Taeeumjowi-tang in Obese Korean Adults: A Double-Blind, Randomized, and Placebo-Controlled Pilot Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/498935 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Sunju Park ◽

Won Nahmkoong ◽

ChunHoo Cheon ◽

Jeong-Su Park ◽

Bo-Hyoung Jang ◽

...

Keyword(s):

Body Fat ◽

Statistical Significance ◽

Pilot Trial ◽

Efficacy And Safety ◽

Initial Weight ◽

Anthropometric Parameters ◽

Related Factors ◽

Double Blind ◽

Significant Difference ◽

Fat Composition

Objective. The purpose of this study was to assess the efficacy and safety of Taeeumjowi-tang (TJ001) as well as to estimate obesity-related factors.Methods. This was a 12-week trial with 5 visits. A total of 102 participants of both genders were randomized to either TJ001 (n=57) group or the placebo group (n=55). Subjects were administered 7 g of either TJ001 or placebo 3 times a day. The primary outcome was a rate of subjects who lost 5% or more of initial weight. Secondary outcomes included anthropometric parameters, lipid profiles, and body fat composition.Results. The subject response rate of ≥5% weight loss compared to baseline was similar in both groups, and no statistically significant difference was observed (P=0.87). Changes in anthropometric parameters were greater during the first 4 weeks in the treatment group (P<0.0001). There were no significant changes in both within groups and between groups for lipid profile and body fat composition. No adverse event was reported in either group.Conclusion. Although the difference between the groups regarding a rate of subjects who lost 5% or more of initial weight did not show statistical significance, TJ001 appears to be beneficial in safely controlling weight.

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Association Between Salivary Flow Rate and the Use of Systemic Medication Among 76-, 81-, and 86-year-old Inhabitants in Helsinki, Finland

Journal of Dental Research ◽

10.1177/00220345920710120401 ◽

1992 ◽

Vol 71 (12) ◽

pp. 1875-1880 ◽

Cited By ~ 116

Author(s):

T.O. Narhi ◽

J.H. Meurman ◽

A. Ainamo ◽

J.M. Nevalainen ◽

K.G. Schmidt-Kaunisaho ◽

...

Keyword(s):

Flow Rate ◽

Age Groups ◽

Salivary Flow ◽

Salivary Flow Rate ◽

Flow Rates ◽

Systemic Medication ◽

Younger Age ◽

Significant Difference ◽

The Difference ◽

Saliva Flow

The aim of this study was to examine salivary flow rate and its association with the use of medication in a representative sample of 76-, 81-, and 86-year-old subjects, totaling 368. In this study, 23% (n = 80) of the subjects were unmedicated. From one to three daily medications were used by 47% (n = 168) and more than four medications by 30% (n = 104). The most commonly used medications were nitrates, digitalis or anti-arrhythmic drugs (47.7%), analgesics and antipyretics (32.6%), and diuretics (29.5%). The mean number used daily was significantly higher in 86-year-olds than in the two younger age groups (p < 0.01). No significant differences in this respect were found between genders. Among the unmedicated subjects, 76-year-olds had significantly higher stimulated salivary flow rates than did the 81-year-olds (p < 0.05). Unmedicated women showed significantly lower unstimulated (p < 0.01) and stimulated flow rates than did men (p < 0.05). Stimulated salivary flow rate was also significantly higher in the 76-year-old medicated subjects than in the medicated 86-year-old subjects (p < 0.05). No statistically significant differences were found in unstimulated salivary flow rates among the three age groups. Medicated women showed significantly lower unstimulated salivary flow rates than men (p < 0.001), although the difference in stimulated saliva flow was not significant. A statistically significant difference in unstimulated and stimulated salivary flow rates was found between unmedicated persons and those who took from four to six, or more than seven, prescribed medications daily.

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A phase II, randomized, double blind comparison of calcium aluminosilicate clay (CASAD) versus placebo (dibasic calcium carbonate) for the prevention of diarrhea in patients (pts) with metastatic colorectal cancer (mCRC) treated with irinotecan (I).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.3600 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 3600-3600

Author(s):

Bryan K. Kee ◽

Rebecca Slack ◽

Todd S. Crocenzi ◽

Lucas Wong ◽

Benjamin Esparaz ◽

...

Keyword(s):

Phase Ii ◽

Performance Status ◽

Symptom Burden ◽

Active Metabolites ◽

Serious Adverse Events ◽

Double Blind ◽

Significance Level ◽

Significant Difference ◽

Grade 3

3600 Background: CASAD is a naturally occurring calcium montmorrilonite clay that serves as a cation exchange absorbent. One of the active metabolites of Irinotecan is SN-38, which is adsorbed by CASAD in vitro. The study hypothesis was that oral CASAD would reduce the rate of grade 3/4 diarrhea in mCRC patients treated with irinotecan. Methods: The study is a multicenter, prospective, randomized, double blinded placebo-controlled phase II trial. One hundred patients receiving I-based chemotherapy were randomized equally between CASAD (1000 mg po 4x daily) and placebo in order to have 75% power to detect a difference in the proportions of patients with grade 3/4 diarrhea within 6 weeks at a 1-sided 5% significance level. We also compared symptom burden using the MDASI questionnaire summed over the 13 symptom items for weeks 0, 3, 5, and 6. Results: Between 5/2009 and 5/2012, 100 patients were randomized in a 1:1 ratio between study arms. Median age 57 yrs, 54% male, 74% Non-Hispanic White, 93% performance status 0 or 1. Serious diarrhea was less frequent than expected based upon prior studies with Irinotecan. In evaluable patients, no significant difference in the rate of G3/4 diarrhea was seen (the primary endpoint): CASAD arm: 7/43 pts (16%), Placebo arm: 3/32 pts (9%), p=0.70. The rate of any diarrhea among all pts was also similar: CASAD arm 64% vs. Placebo arm 70%. The rate of study dropout was 14% in CASAD and 38% for placebo (p=0.01; 2-sided). No differences were found in symptom burden or individual symptom items or serious adverse events. Conclusions: Compared with placebo, CASAD use was safe but ineffective in preventing diarrhea in mCRC patients treated with irinotecan-containing chemotherapy regimens. There were no favorable or unfavorable signals in terms of the patient experience related to symptoms, but there were significantly more dropouts in the placebo arm. Future CASAD trials are focused on active treatment of diarrhea. Clinical trial information: NCT00748215.

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