Prevention of Cisplatin-Induced Emesis by the Oral Neurokinin-1 Antagonist, MK-869, in Combination With Granisetron and Dexamethasone or With Dexamethasone Alone

2001 ◽  
Vol 19 (6) ◽  
pp. 1759-1767 ◽  
Author(s):  
Daniel Campos ◽  
Jose Rodrigues Pereira ◽  
Rick R. Reinhardt ◽  
Carlos Carracedo ◽  
Sergio Poli ◽  
...  
Keyword(s):  
High Dose ◽  
Delayed Emesis ◽  
Double Blind ◽  
Acute Emesis ◽  
Group Iii ◽  
Group I ◽  
Efficacy Parameter ◽  
Group Ii ◽  
Neurokinin 1 ◽  
Present Trial

PURPOSE: The NK1-receptor antagonist MK-869 (L-754,030) has demonstrated antiemetic activity in humans receiving chemotherapy. Objectives of the present trial included the first assessment of oral MK-869 plus dexamethasone compared with a 5HT3 antagonist plus dexamethasone for prevention of acute and delayed emesis after high-dose cisplatin. Furthermore, the study sought to confirm that addition of MK-869 to a 5HT3 antagonist plus dexamethasone was more effective than just the 5HT3 antagonist plus dexamethasone for prevention of acute and delayed emesis. METHODS: This multicenter, double-blind, parallel-group trial in 351 cisplatin-naïve patients evaluated prevention of acute (0 to 24 hours) and delayed emesis (primary efficacy parameter; days 2 to 5) after cisplatin (≥70 mg/m2). Patients were randomized to four groups (I to IV) (n = number randomized; number evaluable): granisetron (10 μg/kg intravenously) pre-cisplatin followed by placebo on days 2 to 5 (group I) (n = 90; 90); granisetron and MK-869 (400 mg PO [by mouth]) pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group II) (n = 86; 84); MK-869 (400 mg PO) the evening before and pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group III) (n = 89; 88); or MK-869 (400 mg PO) pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group IV) (n = 86; 84). All patients also received dexamethasone (20 mg PO) before cisplatin. Additional medication was available to treat emesis or nausea at any time. RESULTS: In the acute period, 57%, 80%, 46%, and 43% of patients were without emesis in groups I, II, III, and IV, respectively (P < .01 for group II v group I). In the delayed period, the proportion of patients without emesis in groups I, II, III, and IV was 29%, 63%, 51%, and 57%, respectively (P < .01 for groups II, III, and IV v group I). The distribution of nausea scores in the delayed period was lower when comparing group II with group I (P < .05 for days 1 to 5 and days 2 to 5). One serious adverse event (dizziness) was rated as possibly related to MK-869. CONCLUSION: Once daily oral administration of MK-869 was effective in reducing delayed emesis and nausea after high-dose cisplatin. However, the combination of the 5HT3 antagonist plus dexamethasone was numerically superior to MK-869 plus dexamethasone in reducing acute emesis. Confirming and extending previous findings, the triple combination of a 5HT3 antagonist, MK-869, and dexamethasone provided the best control of acute emesis.

Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo.

1995 ◽  
Vol 13 (9) ◽  
pp. 2408-2416 ◽  
Author(s):  
R M Navari ◽  
S Madajewicz ◽  
N Anderson ◽  
N S Tchekmedyian ◽  
W Whaley ◽  
...  
Keyword(s):  
Comparative Trial ◽  
Delayed Emesis ◽  
Double Blind ◽  
Acute Emesis ◽  
Group Iii ◽  
Clinical Difference ◽  
Group I ◽  
Major Response ◽  
Delayed Nausea ◽  
Oral Ondansetron

PURPOSE To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.

Platelet Function Studies in Normal Volunteers and Patients with Angina Pectoris

1979 ◽  
Author(s):  
J.J.C. Jonker ◽  
den G.J.H. Ottolander
Keyword(s):  
Platelet Aggregation ◽  
Angina Pectoris ◽  
Platelet Function ◽  
Normal Range ◽  
Double Blind ◽  
Group Iii ◽  
Platelet Survival ◽  
Group I ◽  
Group Ii

In 30 normal subjects (group I) and in 89 patients with angina pectoris we studied: the platelet survival time (PST), the platelet aggregation test I (PAT I) acc. to Breddin, the platelet aggregation ratio (PAR) acc. to Wu and Hoak and the Filtragometer log TA acc. to Hornstra. The patients were divided in two groups: 46 patients had already been treated for 6 months with Clofibrate (group II) and 43 patients with placebo (group III) in a double blind trial. The average PST (T½) was within the normal range (group I 99 hrs. group II 105,7 hrs.; group III 102,0 hrs.). About 20% of patients of group II and III had abnormally shortened T½. The PAT I was on average abnormal in group II and III (PAT I in group II 2,3; group III 2,7), but group II normalized after 12 months treatment (PAT I 1,85). The PAR was abnormal in group III, while group II was within the normal range (group I 0,87; group II 0,82; group III 0,69). The log TA results were abnormal in group II and III (group I 2, 45, group II 2,1; group III 2, 1), after 12 months treatment the patient group remained abnormal (group II 2,2; group III 2,1). We failed to find a correlation between the four platelet function tests, nor with these tests and basic laboratory values. The PAT I, the PAR and the Filtragometer seems to be valuable in the detection of abnormal platelet behavior in vitro, but it does not mean than an abnormal platelet survival in vivo occurs in the same individuals.

Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 546-554 ◽  
Author(s):  
KM Sullivan ◽  
RP Witherspoon ◽  
R Storb ◽  
P Weiden ◽  
N Flournoy ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Aseptic Necrosis ◽  
Actuarial Survival ◽  
Double Blind ◽  
Host Disease ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Recurrent Malignancy ◽  
Blind Comparison

We conducted a randomized, double-blind comparison of prednisone and placebo (group I) v prednisone and azathioprine (1.5 mg/kg/day) (group II) as early treatment of extensive chronic graft-v-host disease (GVHD). Patients with platelet counts less than 100,000/microL were placed into therapy with prednisone alone (group III). All three groups received identical doses of prednisone (1 mg/kg every other day) and one double-strength trimethoprim-sulfamethoxazole (TMP-SMX) tablet twice daily. Between January 1980 and December 1983, 179 previously untreated patients were enrolled and 164 were evaluable. Patients randomized to group I (n = 63) and group II (n = 63) were well matched for prognostic factors; those placed into group III (n = 38) had more frequent acute GVHD and progressive onset of chronic GVHD. Median duration of therapy was 2 years. Complications included diabetes (5%), aseptic necrosis (5%) and infection. For groups I, II, and III, the respective incidence of infection was disseminated varicella, 11%, 24%, 34%; bacteremia, 6%, 11%, 34%; and interstitial pneumonia, 5%, 14%, 18%. Recurrent malignancy was the most frequent cause of death and did not differ significantly across the groups. Nonrelapse mortality, however, did differ: 21% in group I, 40% in group II, and 58% in group III (I v II, P = .003; I v III, P = .001). Forty patients in group I, 30 in group II, and 10 in group III survive with a minimum follow-up of 3.8 years. Karnofsky performance scores for 68 survivors are 90% to 100%, scores for seven survivors are 70% to 89% and scores for five survivors are less than 70%. Actuarial survival at 5 years after transplant is 61% in group I, 47% in group II, and 26% in group III (I v II, P = .03; I v III, P = .0001). Treatment with prednisone alone results in fewer infections and better survival than prednisone and azathioprine in standard-risk chronic GVHD. Treatment with prednisone alone is less effective in high-risk patients with thrombocytopenia, and other strategies are required.

scholarly journals Screening of anticonvulsant effect of carvedilol on electrically induced convulsions in Wistar albino rats

2020 ◽  
Vol 9 (12) ◽  
pp. 1803
Author(s):  
Biacin Babu ◽  
Madhavrao Chavan
Keyword(s):  
Albino Rats ◽  
High Dose ◽  
Anticonvulsant Effect ◽  
Low Doses ◽  
Test Drug ◽  
Group Iii ◽  
Group I ◽  
Significant Difference ◽  
Group Ii ◽  
Wistar Albino Rats

Background: Epilepsy is one of the major central nervous system disorders. The parent study aimed to screen the anticonvulsant effect of carvedilol on electrically induced convulsions in Wistar albino rats.Methods: This study was done in Wistar albino rats. A total of 30 rats were divided into 6 groups each of six rats. group-I (0.9% normal saline), group-II diphenylhydantoin (10 mg/kg/BW/ip), group-III carvedilol (1mg/kg/BW/PO), group-IV carvedilol (2 mg/kg/BW/PO) and group-V carvedilol (4 mg/kg/BW/PO). All the groups were administered drugs and subjected to electric shock. Scores of seizures and percentage of protection were recorded to compare between the groups. One was ANOVA (post hoc) followed by Dunnet t test applied to find the statistically significant between the groups.Results: Group-I showed significant difference compared to other groups. Group-II showed significant difference with group-III and IV not with V. High dose of test drug and standard drug showed similar results in percentage of seizures prevention. Control and low doses of test drugs showed significant difference compared to standard and high dose of test drug in seizures prevention.Conclusions: High of carvedilol showed significant seizures prevention compared to low doses and control group.

scholarly journals Comparison of various regimens of itraconazole in treatment of acute vulvovaginal candidiasis

2021 ◽  
Vol 8 (2) ◽  
pp. 244-249
Author(s):  
Dhiraj Dhoot ◽  
Piyush Prabhat ◽  
Lalita Mayadeo ◽  
Harshal Mahajan
Keyword(s):  
Signs And Symptoms ◽  
Vulvovaginal Candidiasis ◽  
High Dose ◽  
Group Iii ◽  
Group I ◽  
Comparative Clinical Study ◽  
Current Scenario ◽  
Striking Change ◽  
Group Ii ◽  
Cure Rates

One of the most striking change in the current scenario is the increasing occurrence of non-albicans vulvovaginal candidiasis (VVC), which is considered as the major cause of recurrence, relapse and chronic VVC in India. In the present study we evaluated the effectiveness of three different regimens of itraconazole in the treatment of acute VVC.The present randomised, three arm comparative clinical study involved 123 women aged 18 years or above with symptomatic acute VVC. These patients were randomised (41 patients in each group) to receive either itraconazole 200 mg twice daily for 1 day (group I), 200 mg twice daily for 2 days (group II) or 100 mg twice daily for 3 days (group III). Effectiveness was evaluated on the basis of clinical cure (total symptom score), mycological cure (negative KOH test). All the groups were effective in relieving signs and symptoms (p&#60;0.05), but on comparison between all groups, there was statistical difference between Group II and Group I & III (p&#60;0.05) and Group III & I (p&#60;0.05). Complete cure i.e. disappearance of signs and symptoms and negative KOH test was maximum in group II (44%) as compared to groups I (12%) and III (17% of the patients). Relapse was least in seen in 11 patients (27%) in Group I, 3 patients (7%) in Group II and 7 patients (17%) in Group III. All the 3 regimens were well tolerated.In the present study, 2 day high dose itraconazole therapy was found to have better effectiveness compared to conventional regimens. Longer duration of therapy might be required to attain even better cure rates, especially when the incidence of Non Albicans vulvovaginal candidiasis is rising in all parts of the country.

scholarly journals Comparing the effects of dezocine with lidocaine on prevention of propofol injection pain in adults: a prospective randomized double-blind trial

2019 ◽  
Author(s):  
Xuqin Zhu ◽  
Songlin Jia ◽  
Yajun Xu ◽  
Zhirong Sun
Keyword(s):  
Lower Incidence ◽  
Elective Surgery ◽  
Group Iv ◽  
Patient Comfort ◽  
Injection Pain ◽  
Double Blind ◽  
Group V ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Abstract Background Propofol injection pain (PIP) is common and may decrease patient comfort. The aim of this study was to compare the effects of dezocine with lidocaine on prevention of PIP. Methods 235 patients, who scheduled for elective surgery, aged 18-80 years and ASA (American Society of Anesthesiologists) I or II, were randomly assigned into five groups (n = 47 each). All patients were induced through the dor­sal hand vein or antecubital vein. The five groups were given the following medication intravenously: saline (Group I), lidocaine 20 mg (Group II), lidocaine 40 mg (Group III), dezocine 2 mg (Group IV) and dezocine 4 mg (Group V). Twenty seconds later all patients received a propofol infusion and were asked to grade pain or discomfort in the hand or forearm according to a four-point scale until anesthesia. Results Three groups showed a significantly lower incidence of total PIP than Group I: Group III (OR (Odds ratio): 0.39 (0.16, 0.93)); Group IV (OR: 0.21 (0.09, 0.51)) and Group V (OR: 0.12 (0.05, 0.30)). Group IV showed a significantly lower incidence of total PIP than Group II (OR: 0.32 (0.13, 0.77)). Group V showed a significantly lower incidence of total PIP than Group II (OR: 0.15 (0.06, 0.39)) or Group III (OR: 0.30 (0.13, 0.72)). Conclusion Dezocine is a novel agent to alleviate PIP and appears to be more effective than lidocaine.

scholarly journals Comparing the effects of dezocine with lidocaine on prevention of propofol injection pain in adults: a prospective randomized double-blind trial

2019 ◽  
Author(s):  
Xuqin Zhu ◽  
Songlin Jia ◽  
Yajun Xu ◽  
Zhirong Sun
Keyword(s):  
Lower Incidence ◽  
Elective Surgery ◽  
Group Iv ◽  
Patient Comfort ◽  
Injection Pain ◽  
Double Blind ◽  
Group V ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Abstract Background Propofol injection pain (PIP) is common and may decrease patient comfort. The aim of this study was to compare the effects of dezocine with lidocaine on prevention of PIP.Methods 235 patients, who scheduled for elective surgery, aged 18–80 years and American Society of Anesthesiologists (ASA) I or II, were randomly assigned into five groups (n = 47 each). All patients were induced through the dor­sal hand vein or antecubital vein. The five groups were given the following medication intravenously: saline (Group I), lidocaine 20 mg (Group II), lidocaine 40 mg (Group III), dezocine 2 mg (Group IV) and dezocine 4 mg (Group V). Twenty seconds later all patients received a propofol infusion and were asked to grade pain or discomfort in the hand or forearm according to a four-point scale until anesthesia.Results Three groups showed a significantly lower incidence of total PIP than Group I: Group III (OR [Odds ratio]: 0.39 (0.16, 0.93)); Group IV (OR: 0.21 (0.09, 0.51)) and Group V (OR: 0.12 (0.05, 0.30)). Group IV showed a significantly lower incidence of total PIP than Group II (OR: 0.32 (0.13, 0.77)). Group V showed a significantly lower incidence of total PIP than Group II (OR: 0.15 (0.06, 0.39)) or Group III (OR: 0.30 (0.13, 0.72)).Conclusion Dezocine is a novel agent to alleviate PIP and appears to some extent to be more effective than lidocaine.

High-Dose Ascorbic Acid Decreases Cholesterolemic Factors of an Atherogenic Diet in Guinea Pigs

2007 ◽  
Vol 77 (2) ◽  
pp. 125-129
Author(s):  
Filis ◽  
Anastassopoulou ◽  
Sigala ◽  
Theodorou ◽  
Manouras ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Guinea Pigs ◽  
Low Dose ◽  
Plasma Concentrations ◽  
Atherogenic Diet ◽  
High Dose ◽  
Low Density ◽  
Group Iii ◽  
Group I ◽  
Group Ii

Background: The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Methods: Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Results: Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). Conclusion: High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Prevention of chemotherapy-induced delayed nausea and vomiting with aprepitant in patients recieving highly emetogenic-five day cisplatin regimens

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14125-14125 ◽  
Author(s):  
A. J. Joshi ◽  
H. Singh ◽  
S. Chawla
Keyword(s):  
Small Sample Size ◽  
Rescue Therapy ◽  
Small Sample ◽  
P Value ◽  
High Dose ◽  
Delayed Emesis ◽  
End Point ◽  
Group I ◽  
Delayed Nausea ◽  
Group Ii

14125 Background: It has been shown that addition of the NK1 receptor antagonist aprepitant to 5HT3 antagonist plus dexamethasone is more effective than just the 5HT3 antagonist plus dexamethasone for prevention of acute and delayed emesis due to high dose cisplatin and also that this effect lasts for multiple cycles. This study evaluated whether the antiemetic efficacy of aprepitant could be sustained for 5 day cisplatin regimens. Methods: Patients receiving cisplatin 20mg/m2/day for 5 days (PEB and TCF regimens ) were randomized to one of the following two regimens: (1) aprepitant 125 mg 1 hour before cisplatin on day 1 and aprepitant 80 mg on days 2 and 3 (n = 17); (2) placebo before cisplatin on days 2 to 7 (n = 19). All groups received ondansetron 32 mg and dexamethasone 20 mg before cisplatin, and dexamethasone 8 mg on days 2 to 7. The primary end point was complete response (no emesis and no rescue therapy) over 7 days following cisplatin in up to six cycles analyzed by a modified intent-to-treat approach. Secondary end point was evaluated using Functional Living Index-Emesis questionnaire. Treatment comparisons were made using logistic regression models and P value calculated using the chi square test due to small sample size. Results: In the acute period, 83% and 56% of patients were without emesis in groups I and II, respectively (P < .01 for group I v group II). In the delayed period upto day 5, the proportion of patients without emesis in groups I and II, was 59% and 32%, respectively (P < .01 for groups I v group II). In the extended period day 6 and 7 the proportion of patients without emesis in groups I and II was 50% and 38% respectively (P< .01 for groups I v II). The distribution of nausea scores in the delayed period beyond day 5 was lower when comparing group I with group II (P < .05 for days 6 and 7). Two serious adverse events of diarrhea were probably attributed to aprepitant. Conclusions: Once daily oral administration of aprepitant was effective and superior in reducing delayed emesis and nausea after 5 days cisplatinum regimen when added to 5HT3 antagonist plus dexamethasone. This benefit persists upto day 7. Confirming and extending previous results aprepitant should be used in triple combination in patients receiving 5 day cisplatin regimens. No significant financial relationships to disclose.

Aspirin, Dipyridamole and Platelet Survival in Patients with Diabetes Mellitus

1982 ◽  
Vol 63 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Hilary Tindall ◽  
R. Colin Paton ◽  
George P. McNicol
Keyword(s):  
Diabetic Patients ◽  
High Dose ◽  
Double Blind ◽  
Regeneration Time ◽  
Dose Aspirin ◽  
Platelet Survival ◽  
Group I ◽  
The Mean ◽  
Group Ii ◽  
High Dose Aspirin

1. Platelet survival in 27 insulin-dependent diabetic patients with severe retinopathy was studied in a double-blind cross-over trial using placebo, aspirin (990 mg/day) and a combination of dipyridamole (225 mg/day) with aspirin at two dosage levels (330 mg and 990 mg/day). 2. Twenty patients (group I) had 51Cr-labelled-platelet survival after treatment with placebo and the high-dose-aspirin/dipyridamole combination. The remaining seven patients (group II) had platelet-regeneration times measured after each of the four treatment periods. 3. Treatment of group I patients with the high-dose-aspirin/dipyridamole combination resulted in significant (P < 0·001) prolongation of platelet survival from 7·3 ± 0·2 (mean ± sem) days to 8·4 ± 0·1 days. 4. In group II patients, when compared with the mean placebo result of 7·2 ± 0·2 days, the mean aspirin-labelled-platelet-regeneration time was significantly (P < 0·01) longer only after high-dose-aspirin/dipyridamole (9·8 ± 0·5 days) but not after low-dose-aspirin/dipyridamole (8·3 ± 0·5 days) or aspirin alone (7·3 ± 0·3 days). 5. These results suggest that it may be premature to consider reducing the dose of aspirin in aspirin/dipyridamole combinations below 1 g/day when used as antithrombotic therapy.

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