scholarly journals Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Toxicity of Subcutaneous Ketamine in the Management of Cancer Pain

2012 ◽  
Vol 30 (29) ◽  
pp. 3611-3617 ◽  
Author(s):  
Janet Hardy ◽  
Stephen Quinn ◽  
Belinda Fazekas ◽  
John Plummer ◽  
Simon Eckermann ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Positive Outcome ◽  
Phase Iii ◽  
Additional Patient ◽  
Controlled Study ◽  
Net Benefit ◽  
Primary Analysis ◽  
Double Blind ◽  
Number Of Patients ◽  
Significant Difference

Purpose The anesthetic ketamine is widely used for pain related to cancer, but the evidence to support its use in this setting is weak. This study aimed to determine whether ketamine is more effective than placebo when used in conjunction with opioids and standard adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered of net benefit if it provided clinically relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity. Patients and Methods In this multisite, dose-escalation, double-blind, randomized, placebo-controlled phase III trial, ketamine or placebo was delivered subcutaneously over 3 to 5 days. Results In all, 185 participants were included in the primary analysis. There was no significant difference between the proportion of positive outcomes (0.04; 95% CI, −0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27% [25 of 92] and 31% [29 of 93]). Pain type (nociceptive v neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (incidence rate ratio, 1.95; 95% CI, 1.46 to 2.61; P < .001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00 to 1.18; P = .039). The number of patients needed to treat for one additional patient to have a positive outcome from ketamine was 25 (95% CI, six to ∞). The number needed to harm, because of toxicity-related withdrawal, was six (95% CI, four to 13). Conclusion Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard coanalgesics in cancer pain.

scholarly journals A randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2604-2604
Author(s):  
David C Currow ◽  
Janet Hardy ◽  
Stephen Quinn ◽  
Belinda Fazekas ◽  
John Plummer ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Cochrane Review ◽  
Positive Outcome ◽  
Phase Iii ◽  
Additional Patient ◽  
Controlled Study ◽  
Number Needed To Treat ◽  
Net Benefit ◽  
Double Blind ◽  
Significant Difference

2604 Background: The dissociative anaesthetic ketamine is widely used for cancer related pain. A Cochrane review concluded that insufficient evidence was available to support its use in this setting. Methods: This phase III, multisite, double-blind, dose escalation, placebo, randomised controlled study aimed to determine whether ketamine, delivered subcutaneously over three to five days is more effective than placebo, when used in conjunction with adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered to be of net benefit if it provided a reduction in average pain scores by ≥2/10 points from baseline, with limited breakthrough analgesia and acceptable toxicity. Results: For the 185 participants, there was no significant difference between the proportion of positive outcomes (0.04 (-0.10, 0.18) p=0.55) in the placebo and intervention arms (response rates 27% (25/92) and 31% (29/93)). Pain type (nociceptive versus neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (IRR = 1.95 (1.46, 2.61), p<0.001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event/day (OR=1.09 (1.00, 1.18), p=0.039). The number needed to treat for one additional patient to get a positive outcome from ketamine was 25 (6, ∞). The number needed to harm, because of toxicity-related withdrawal was 6 (4, 13). Conclusions: Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard co-analgesics in cancer pain.

Economic evaluation of the randomised, double-blind, placebo-controlled study of subcutaneous ketamine in the management of chronic cancer pain

2018 ◽  
Vol 33 (1) ◽  
pp. 74-81 ◽  
Author(s):  
Nikki McCaffrey ◽  
Thomas Flint ◽  
Billingsley Kaambwa ◽  
Belinda Fazekas ◽  
Debra Rowett ◽  
...  
Keyword(s):  
Palliative Care ◽  
Cost Effectiveness ◽  
Cancer Pain ◽  
Sensitivity Analyses ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Cost Effective Treatment ◽  
Significant Difference ◽  
The Cost

Background: Treating chronic, uncontrolled, cancer pain with subcutaneous ketamine in patients unresponsive to opioids and co-analgesics remains controversial, especially in light of recent evidence demonstrating ketamine does not have net clinical benefit in this setting. Aim: To evaluate the cost-effectiveness of subcutaneous ketamine versus placebo in this patient population. Design and setting: A within-trial cost-effectiveness analysis of the Australian Palliative Care Clinical Studies Collaborative’s randomised, double-blind, placebo-controlled trial of ketamine was conducted from a healthcare provider perspective. Mean costs and outcomes were estimated from participant-level data over 5 days including positive response, health-related quality of life (HrQOL) measured with the Functional Assessment of Chronic Illness Therapy–Palliative Care (FACIT-Pal), ketamine costs, medication usage and in-patient stays. Results: There was no statistically significant difference in responder rates, but higher toxicity and worse HrQOL for ketamine participants (mean change −3.10 (standard error (SE) 1.76), ketamine n = 93; 4.53 (SE 1.38), placebo n = 92). Estimated total mean costs were AU$706 higher per ketamine participant (AU$6608) compared with placebo (AU$5902), attributable to the cost of higher in-patient costs as well as costs of ketamine administration. The results were robust to sensitivity analyses accounting for different medication use costing methods and removal of cost outliers. Conclusion: The findings suggest subcutaneous ketamine in conjunction with opioids and standard adjuvant therapy is neither an effective nor cost-effective treatment for refractory pain in advanced cancer patients.

Efficacy of Phenazone in the Treatment of Acute Migraine Attacks: A Double-Blind, Placebo-Controlled, Randomized Study

Cephalalgia ◽  
2004 ◽  
Vol 24 (10) ◽  
pp. 888-893 ◽  
Author(s):  
H Göbel ◽  
A Heinze ◽  
U Niederberger ◽  
T Witt ◽  
V Zumbroich
Keyword(s):  
Adverse Events ◽  
Randomized Study ◽  
Controlled Study ◽  
Acute Migraine ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Number Of Patients ◽  
Significant Difference ◽  
Main Target

In this study we compared the efficacy of 1000 mg phenazone with that of placebo in the treatment of acute migraine attacks in a randomized double-blind, placebo-controlled study of 208 patients. The main target criterion was the number of patients with a pain reduction from severe or moderate to slight or no pain 2 h after taking the pain medication. The percentage of patients satisfying the main target criterion was 48.6% for phenazone and 27.2% ( P < 0.05) for placebo. Freedom from pain after 2 h was reported by 27.6% with phenazone treatment and 13.6% ( P < 0.05) with placebo. Compared with placebo, the phenazone treatment also resulted in a significant improvement in the associated migraine symptoms of nausea, phonophobia and photophobia. Of patients treated with phenazone 11.4%, and 5.8% of those treated with placebo reported adverse events. There was no significant difference between the groups with regard to numbers of patients with adverse events. No serious adverse events occurred. The results show that phenazone at a dosage of 1000 mg is effective and well tolerated in the treatment of acute migraine attacks.

scholarly journals Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Long-Acting Methylphenidate for Cancer-Related Fatigue: North Central Cancer Treatment Group NCCTG-N05C7 Trial

2010 ◽  
Vol 28 (23) ◽  
pp. 3673-3679 ◽  
Author(s):  
Amanda R. Moraska ◽  
Amit Sood ◽  
Shaker R. Dakhil ◽  
Jeff A. Sloan ◽  
Debra Barton ◽  
...  
Keyword(s):  
Short Form ◽  
Phase Iii ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Symptom Experience ◽  
Double Blind ◽  
Time Curve ◽  
Cancer Related Fatigue ◽  
Significant Difference ◽  
Long Acting

Purpose Fatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities. Patients and Methods Adults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change. Results In total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm. Conclusion This clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.

INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG), first results.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 9-9 ◽  
Author(s):  
Nick Pavlakis ◽  
Katrin Marie Sjoquist ◽  
Eric Tsobanis ◽  
Andrew Martin ◽  
Yoon-Koo Kang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Secondary Analysis ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Prognostic Indicators ◽  
Controlled Study ◽  
Primary Analysis ◽  
Double Blind

9 Background: Advanced Oesophago-Gastric Carcinoma (AOGC) has limited options following failure of first or second line chemotherapy (CT). Regorafenib (REG) is an oral multi-kinase inhibitor of kinases involved in angiogenesis, tumor microenvironment, and oncogenesis. This study examined whether REG has sufficient activity and safety for further evaluation. Methods: International (Australia & New Zealand (ANZ), Korea, Canada (NCIC CTG)) randomised phase II trial with 2:1 randomisation and stratification by: (1) Lines of prior CT for advanced disease (1 vs. 2) and (2) Region. Eligible patients received best supportive care plus 160mg REG or matching PBO orally on days 1-21 each 28-day cycle until disease progression or prohibitive adverse events. Primary endpoint was progression free survival (PFS) in the REG arm, assuming median 8 weeks (wks) in PBO arm, aiming for 13.2 wks with REG to be of interest. Results: From Nov 2012 to Feb 2014, 152 patients were enrolled, 147 evaluable [pre-specified primary analysis population]: (REG n=97: PBO n=50); well matched for key baseline prognostic indicators; male:female (118:29); primary location: OG Junction (56), stomach (85); lines of prior therapy: 1 (63), 2 (84); ECOG 0 (62): 1 (85). Time on treatment: Median: 7.9 (REG) v 4 (PBO) wks. In the evaluable population median PFS was 11.1 wks (95% CI: 7.7 - 12.3) (REG) and 3.9 wks (95% CI: 3.7 - 4.0) (PBO), log-rank p <0.0001; HR 0.41 (95% CI: 0.28 to 0.59). PFS results were maintained for secondary analysis including all randomized patients (n = 152). REG was well tolerated, with the spectrum of toxicity in keeping with previous reports. Conclusions: PFS was clearly significantly longer with REG than PBO, though PBO PFS was less than anticipated. The pre-specified exploratory comparisons provide compelling evidence that REG has sufficient activity with acceptable tolerability in refractory AOGC to warrant phase III evaluation. Mature OS results will be presented at the meeting. Clinical trial information: 12612000239864.

A phase III randomized, double-blind placebo controlled study of armodafinil (Nuvigil) to reduce cancer-related fatigue in patients with high-grade glioma (Alliance A221101).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12007-12007
Author(s):  
Alyx B. Porter ◽  
Heshan Liu ◽  
Sadhna Kohli ◽  
Jane H. Cerhan ◽  
Jeff A. Sloan ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
Phase Iii ◽  
Controlled Study ◽  
High Grade ◽  
Double Blind ◽  
Meaningful Improvement ◽  
Fatigue Score ◽  
Severe Fatigue ◽  
Significant Difference ◽  
Endpoint Data

12007 Background: Up to 96% of patients with high grade glioma (HGG) report moderate to severe fatigue. Armodafinil, the R-enantiomer of modafinil, is a psychostimulant with low potential for abuse that has shown potential for improving severe fatigue in HGG patients. Methods: In this phase III double blinded placebo-controlled study, adults with HGG and moderate to severe fatigue, > 4 weeks after completing radiotherapy, were randomized to receive armodafinil daily (150 mg or 250 mg) or placebo for a total of 8 weeks. The primary outcome was efficacy in treating severe fatigue. Secondary outcomes included evaluation of tolerability, neurocognitive function, and quality of life. Patients were evaluated at baseline, 4 and 8 weeks. Results: A total of 328 patients were enrolled between 6/3/13-3/1/19. There were 103 (150 mg arm), 97 (250 mg arm) and 97 (placebo arm) evaluable patients with primary endpoint data available. The median age was 60 years (20-85) with a median Brief Fatigue Inventory (BFI) worst fatigue score of 8 (6-10). 60.3% were male, 80.5% received concomitant chemotherapy, and 39.7% were on corticosteroids. The global fatigue score at end of weeks 4 and 8 were lower than at baseline (p<0.0001) and in the 250 mg arm than placebo (p=0.0356) and was higher for corticosteroid users than non-users (p=0.0002). There was no statistically significant difference for clinically meaningful improvement in BFI usual fatigue score from baseline to end of week 8 between the three arms (p=0.9601). Patients reported an improvement in concentration at week 4 from baseline on the 150 mg arm(P=0.0311). There was no statistically significant difference on neurocognitive tests from baseline to end of week 4 (p>0.05) or week 8 (p>0.05) between arms. More patients reported insomnia on the 250 mg arm (p=0.0083). Conclusions: There is no meaningful benefit of the use of armodafinil to reduce moderate to severe fatigue in patients with HGG. In certain cases there may be benefit of armodafinil 150 mg to aid concentration without the risk of insomnia.Support: UG1CA189823;U10CA180868 (NRG). Clinical trial information: NCT01781468 .

Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study

2019 ◽  
Vol 54 (3) ◽  
pp. 288-297 ◽  
Author(s):  
Jerome Sarris ◽  
Gerard J Byrne ◽  
Chad A Bousman ◽  
Lachlan Cribb ◽  
Karen M Savage ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Anxiety Reduction ◽  
Phase Iii ◽  
Controlled Study ◽  
Relative Reduction ◽  
Generalised Anxiety Disorder ◽  
Short Term ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Significant Difference

Objective: Previous randomised, double-blind, placebo-controlled studies have shown that Kava (a South Pacific medicinal plant) reduced anxiety during short-term administration. The objective of this randomised, double-blind, placebo-controlled study was to perform a larger, longer-term trial assessing the efficacy and safety of Kava in the treatment of generalised anxiety disorder and to determine whether gamma-aminobutyric acid transporter (SLC6A1) single-nucleotide polymorphisms were moderators of response. Methods: The trial was a phase III, multi-site, two-arm, 16-week, randomised, double-blind, placebo-controlled study investigating an aqueous extract of dried Kava root administered twice per day in tablet form (standardised to 120 mg of kavalactones twice/day) in 171 currently non-medicated anxious participants with diagnosed generalised anxiety disorder. The trial took place in Australia. Results: An analysis of 171 participants revealed a non-significant difference in anxiety reduction between the Kava and placebo groups (a relative reduction favouring placebo of 1.37 points; p = 0.25). At the conclusion of the controlled phase, 17.4% of the Kava group were classified as remitted (Hamilton Anxiety Rating Scale score < 7) compared to 23.8% of the placebo group ( p = 0.46). No SLC6A1 polymorphisms were associated with treatment response, while carriers of the rs2601126 T allele preferentially respond to placebo ( p = 0.006). Kava was well tolerated aside from poorer memory (Kava = 36 vs placebo = 23; p = 0.044) and tremor/shakiness (Kava = 36 vs placebo = 23; p = 0.024) occurring more frequently in the Kava group. Liver function test abnormalities were significantly more frequent in the Kava group, although no participant met criteria for herb-induced hepatic injury. Conclusion: While research has generally supported Kava in non-clinical populations (potentially for more ‘situational’ anxiety as a short-term anxiolytic), this particular extract was not effective for diagnosed generalised anxiety disorder.

Randomised, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naïve patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): BO17704

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA7514-LBA7514 ◽  
Author(s):  
C. Manegold ◽  
J. von Pawel ◽  
P. Zatloukal ◽  
R. Ramlau ◽  
V. Gorbounova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Logrank Test ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Multicentre Phase ◽  
Number Of Patients ◽  
Phase Iii Study

LBA7514 Background: The ECOG 4599 phase III trial demonstrated that the addition of bevacizumab (B) to carboplatin/paclitaxel improved overall and progression-free survival (PFS) in patients (pts) with advanced NSCLC [Sandler et al. NEJM 2006]. Cisplatin/gemcitabine (CG) is a common combination in regions outside of the US. Methods: This randomised, placebo-controlled phase III study compared two doses of B plus CG versus CG plus placebo. The primary endpoint was PFS; secondary endpoints include overall survival, response rate (RR) and safety. Eligibility criteria: histologically or cytologically documented previously untreated advanced or recurrent non- squamous NSCLC; ECOG PS 0–1; no brain metastases. Between 2/05 and 8/06 1,043 pts were randomised to: C 80mg/m2 on d1 and G 1,250mg/m2 on d1 and d8 every 3 wks for up to 6 cycles plus B continued to progression at 7.5mg/kg every 3 wks, or 15mg/kg every 3 wks or placebo. The study was designed to include the number of patients required to observe a 30% reduction in the risk of a PFS event in the B arms compared with control using a two-sided logrank test (a=2.5%) with 80% power. Results: PFS was significantly prolonged as analysed both in a primary analysis (without censoring for non-protocol anti-neoplastic therapy [NPT] prior to progression) and in a prespecified analysis with censoring for NPT. The RR and response duration were also increased. Overall survival is immature due to short duration of follow up. Conclusions: Both doses of B significantly improved PFS and RR, consistent with the results of the earlier phase III trial E4599. No unexpected safety signals were detected. [Table: see text] [Table: see text]

Comparing Schizophrenia Patients With a Predicted High/Low Risk of Nonresponse Receiving Treatment with Ziprasidone and Haloperidol: A Randomized-Controlled Study

2018 ◽  
Vol 52 (04) ◽  
pp. 180-185
Author(s):  
Rebecca Schennach ◽  
Michael Riedel ◽  
Ilja Spellmann ◽  
Richard Musil ◽  
Michael Obermeier ◽  
...  
Keyword(s):  
High Risk ◽  
Randomized Study ◽  
Low Risk ◽  
Controlled Study ◽  
Antipsychotic Treatment ◽  
Double Blind ◽  
Syndrome Scale ◽  
Number Of Patients ◽  
Significant Difference ◽  
Negative Syndrome

Abstract Introduction The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. Methods One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). Results Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). Discussion An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.

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