There are 9 clinical trials
This is an open-label, multi-center study designed to extend the evaluation of the safety, tolerability, and clinical effects of oral administration of KNS-760704 in patients with ALS.
Eligible patients will receive 1 tablet of KNS-760704 150 mg every 12 hours (Q12H) (300 mg total daily dose) for up to 180 weeks. --- Q12H ---
This is a phase-II study to evaluate the efficacy of a salvage regimen in children with relapsed T-cell ALL or lymphoma. Peg-asparaginase, mitoxantrone, intrathecal triples (IT) (intrathecal methotrexate/hydrocortisone/cytarabine) (ITMHA) and dexamethasone are commonly used drugs to treat relapsed or refractory acute lymphocytic leukemia or lymphoma (ALL). In this study, the investigators want to know if adding three drugs called panobinostat, bortezomib and liposomal vincristine (VSLI) to this regimen will result in remission (no signs or symptoms of leukemia or lymphoma). - Panobinostat has been approved by the FDA for treating adults with multiple myeloma, but it has not been approved for use in children and has not been given together with the other drugs used in this study. It has not been widely studied in children. - VSLI has been approved by the FDA for adults with relapsed or refractory ALL, but has not yet been approved for treating children with leukemia or lymphoma. - Bortezomib has been approved by the FDA for treating adults with a cancer called multiple myeloma and adults with relapsed mantle cell lymphoma; it has not been approved for treating children. PRIMARY OBJECTIVE: - To estimate the complete remission (CR) rate for patients with T-cell lymphoblastic leukemia and lymphoma in first relapse. SECONDARY OBJECTIVES: - To evaluate minimal residual disease (MRD) levels at end of each block of therapy. - To describe the toxicities of vincristine sulfate liposome injection (VSLI) when used in combination with chemotherapy and bortezomib.
Additional ITs on Days 10 and 17 for patients with central nervous system (CNS) 2, 3 or traumatic tap with blasts Block B: approximately 5 weeks - High-dose methotrexate 8 g/m^2 IV over 24 hours (will not be given to patients with prior cranial irradiation) Day 1 - 6-mercaptopurine 50 mg/m^2 PO days 1-14 - ITMHA Day 1 - High-dose cytarabine 3 g/m^2 IV every 12 hours (Q12H) Days 15 and 16 Block C: approximately 3 weeks - Nelarabine 650 mg/m^2/day IV Days 1-5 (Clofarabine 40 mg/m^2/day IV Days 1-5 will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II) - Cyclophosphamide 300 mg/m^2 IV Days 1-5 - Etoposide 100 mg/m^2/day IV Days 1-5 Response evaluation is performed after the end of each treatment block. --- Q12H ---
Description: All participants who start re-induction Block A therapy are considered evaluable. Any patient who at any time point achieves CR and goes to transplant is considered as a success; or any patient who successfully reaches the end of block C and achieves/remains in CR is considered a success; all other cases are considered as failure.
Measure: Complete Remission (CR) Rate Time: At the end of each remission re-induction block C (approximately 13 weeks after start of therapy)Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
Measure: Block A Minimal Residual Disease (MRD) Time: At the end of Block A therapy (approximately 5 weeks after start of therapy)Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
Measure: Block B Minimal Residual Disease (MRD) Time: At the end of Block B therapy (approximately 10 weeks after start of therapy)Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
Measure: Block C Minimal Residual Disease (MRD) Time: At the end of Block C therapy (approximately 13 weeks after start of therapy)Description: The toxicities of liposomal vincristine (VSLI) when used in combination with chemotherapy will be evaluated. Proportions (probabilities) of relevant toxicities will be estimated with point and interval estimates.
Measure: Proportion of Relevant Toxicities Time: At the completion of therapy (up to approximately 5 months after the start of therapy)The present study is designed to assess the safety and tolerability of escalating, multiple ascending doses of Cavosonstat (N91115) in healthy subjects.
Eligible subjects will be randomized in a 3:1 ratio to receive investigational medicinal product (IMP) N91115 (daily [QD] or every 12 hours [Q12H]) or matching placebo (QD or Q12H) for 7 days and will be followed for safety while housed in the clinical research unit (CRU) until discharge on Day 8. Pharmacokinetics will be followed from Study Day 1 through the morning of Study Day 8. --- Q12H ---
Eligible subjects will be randomized in a 3:1 ratio to receive investigational medicinal product (IMP) N91115 (daily [QD] or every 12 hours [Q12H]) or matching placebo (QD or Q12H) for 7 days and will be followed for safety while housed in the clinical research unit (CRU) until discharge on Day 8. Pharmacokinetics will be followed from Study Day 1 through the morning of Study Day 8. --- Q12H --- --- Q12H ---
Description: Safety assessments based on clinical evaluations, laboratory assessments, and adverse events
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: 14 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in urine.
Measure: Pharmacokinetic parameters of N91115 and metabolites (Amount of analyte excreted in the urine [Ae]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in urine.
Measure: Pharmacokinetic parameters of N91115 and metabolites (% analyte excreted in the urine [Fe]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measure: Pharmacokinetic parameters of N91115 and metabolites (area under the curve [AUC]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measure: Pharmacokinetic parameters of N91115 and metabolites (maximum concentration [Cmax]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in urine and plasma.
Measure: Pharmacokinetic parameters of N91115 and metabolites (clearance [CL]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measure: Pharmacokinetic parameters of N91115 and metabolites (accumulation index [Racc]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measure: Pharmacokinetic parameters of N91115 and metabolites (Terminal elimination half-life [t1/2]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measure: Pharmacokinetic parameters of N91115 and metabolites (time of maximum concentration [Tmax]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measure: Pharmacokinetic parameters of N91115 and metabolites (metabolite to parent exposure ratio [M/P ratio]) Time: 7 daysDescription: Pharmacokinetic parameter of N91115 and metabolites will be measured in plasma.
Measure: Pharmacokinetic parameters of N91115 and metabolites (terminal elimination rate constant [lambda z]) Time: 7 daysDengue fever is an acute febrile illness transmitted by mosquitoes, which affects half the world's population. There are 96 million symptomatic infections, 500,0000 hospitalisations and 25,000 deaths per year attributed to the disease. The economic burden is $12 billion. In Singapore, as elsewhere, the incidence of the disease continues to increase despite aggressive control measures. At present there are no approved medicines for treating dengue fever. Only supportive fluid replacement therapy is used to treat vascular leakage in patients with severe illness. Therefore there is an urgent need to find alternative treatments. Experiments in the laboratory have shown that Celgosivir and modipafant inhibit dengue virus and improve mouse survival. Both drugs have previously been used in humans with good safety records, so investigators are taking this one step further to find out how well it works in dengue patients. Investigators plan to enroll dengue patients within 48 hours of fever onset and assign them to one of four treatment groups over five days. Together with the support from the industry partner, 60°Pharmaceuticals PLC, the investigators will determine the safety and effectiveness of these drugs on acute dengue patients and pave the way forward for dengue antiviral medicines to reach patients.
If a signal is detected, a sample size calculation will be undertaken for Part 2. The Sponsor will convene a Scientific Advisory Board (SAB) who will then review unblinded log10 serum viral load AUC for viraemia and platelet count data to recommend which dosing monotherapy dosing regimen to advance to Part 2. If the recommended sample size for Part 2 exceeds the maximum specified for Part 1 and 2 (a total combined sample size of N = 132 participants) for a monotherapy, the Sponsor will submit a major amendment for Institutional Review Board/ Health Science Authority (IRB/HSA) consideration prior to initiating Part 2. For Part 2, up to 60 otherwise healthy participants with uncomplicated dengue fever meeting the inclusion/exclusion criteria will be assigned in a randomised double-blind fashion to: - Cohort 5: (i) celgosivir monotherapy 150 mg Q6H, OR (ii) modipafant monotherapy (either 50 mg Q12H or 100 mg Q12H) - Cohort 6: Placebo extension for 5 days of treatment. --- Q12H ---
If a signal is detected, a sample size calculation will be undertaken for Part 2. The Sponsor will convene a Scientific Advisory Board (SAB) who will then review unblinded log10 serum viral load AUC for viraemia and platelet count data to recommend which dosing monotherapy dosing regimen to advance to Part 2. If the recommended sample size for Part 2 exceeds the maximum specified for Part 1 and 2 (a total combined sample size of N = 132 participants) for a monotherapy, the Sponsor will submit a major amendment for Institutional Review Board/ Health Science Authority (IRB/HSA) consideration prior to initiating Part 2. For Part 2, up to 60 otherwise healthy participants with uncomplicated dengue fever meeting the inclusion/exclusion criteria will be assigned in a randomised double-blind fashion to: - Cohort 5: (i) celgosivir monotherapy 150 mg Q6H, OR (ii) modipafant monotherapy (either 50 mg Q12H or 100 mg Q12H) - Cohort 6: Placebo extension for 5 days of treatment. --- Q12H --- --- Q12H ---
Description: Area under the curve (AUC) for serum viral load from baseline to Study Day 5 of Celgosivir dosing
Measure: Viral load AUC for viremia Time: Day 1 to Day 5Description: Lowest platelet count recorded from baseline to Study Day 5 of Modipafant dosing
Measure: Platelet nadir Time: Day 1 to Day 5Description: The time from the start of treatment to the start of the first 24-hour period during which the tympanic or oral temperature remains below 37.5°C
Measure: Fever clearance time (days) Time: Day 1 to 28Description: A 24-hour reduction in duration of illness that is treatment related is deemed clinically relevant. Draft criteria to support this include: Absence of fever (< 37.4˚C) for at least 24 hours
Measure: Duration of illness Time: Day 1 to 28Description: Determined by comparison of the maximum haematocrit detected in the acute phase as compared to baseline
Measure: Maximum percentage haemoconcentration Time: Day 1 to 28This is a 6-week randomized, double-blind trial of 4 different non-steroidal anti-inflammatory drugs in patients with axial spondyloarthritis to compare the change of pain score from baseline at 4 weeks to the change of pain score from baseline at 6 weeks.
Ankylosing Spondylitis Axial Spondyloarthritis Spondylitis Spondylitis, Ankylosing Spondylarthritis Patients with ankylosing spondylitis or axial spondyloarthritis who fulfills the inclusion and exclusion criteria will be randomized into one of the four arms after an initial one week washout period, including: 1) indomethacin 75mg Q12H; 2) diclofenac 75mg Q12H; 3) meloxicam 7.5mg Q12H; 4) celecoxib 200mg Q12H. --- Q12H ---
Ankylosing Spondylitis Axial Spondyloarthritis Spondylitis Spondylitis, Ankylosing Spondylarthritis Patients with ankylosing spondylitis or axial spondyloarthritis who fulfills the inclusion and exclusion criteria will be randomized into one of the four arms after an initial one week washout period, including: 1) indomethacin 75mg Q12H; 2) diclofenac 75mg Q12H; 3) meloxicam 7.5mg Q12H; 4) celecoxib 200mg Q12H. --- Q12H --- --- Q12H ---
Ankylosing Spondylitis Axial Spondyloarthritis Spondylitis Spondylitis, Ankylosing Spondylarthritis Patients with ankylosing spondylitis or axial spondyloarthritis who fulfills the inclusion and exclusion criteria will be randomized into one of the four arms after an initial one week washout period, including: 1) indomethacin 75mg Q12H; 2) diclofenac 75mg Q12H; 3) meloxicam 7.5mg Q12H; 4) celecoxib 200mg Q12H. --- Q12H --- --- Q12H --- --- Q12H ---
Ankylosing Spondylitis Axial Spondyloarthritis Spondylitis Spondylitis, Ankylosing Spondylarthritis Patients with ankylosing spondylitis or axial spondyloarthritis who fulfills the inclusion and exclusion criteria will be randomized into one of the four arms after an initial one week washout period, including: 1) indomethacin 75mg Q12H; 2) diclofenac 75mg Q12H; 3) meloxicam 7.5mg Q12H; 4) celecoxib 200mg Q12H. --- Q12H --- --- Q12H --- --- Q12H --- --- Q12H ---
Description: change of pain score by numerical rating score from baseline [scale range: 0 (better) -10 (worse)]
Measure: change of pain score Time: at week 4 vs. at week 6Description: change of Bath Ankylosing Spondylitis Disease Activity Index from baseline [scale range: 0 (better) -10 (worse)]
Measure: change of BASDAI Time: at week 4 vs. at week 6Description: change of Bath Ankylosing Spondylitis Functional Index from baseline [scale range: 0 (better) -10 (worse)]
Measure: change of BASFI Time: at week 4 vs. at week 6Description: change of Ankylosing Spondylitis Disease Activity Score from baseline [composite score: 0 (no disease activity) - 6.5 (very high disease activity)]
Measure: change of ASDAS Time: at week 4 vs. at week 6Description: patient's global assessment of effectiveness of a treatment
Measure: Patient Global Assessment of Response to Therapy (PGART) Time: at week 6A study for women with ovarian cancer that has returned at least 6 months after platinum-based chemotherapy.
The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).. Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin. --- Q12H ---
Description: Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).
Measure: Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD]) Time: Cycle 1 (21 Days)Description: PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Measure: Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin Time: Randomization to Date of Disease Progression or Death from any cause (up to 3 years)Description: Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Measure: Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate) Time: Baseline to Disease Progression (up to 3 years)Description: Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.
Measure: Phase 2: Overall Survival Time: Baseline to Date of Death from any cause (up to 5 years)Description: PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.
Measure: Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820 Time: Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPDDescription: The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = "not at all" and 4 = "very much." Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.
Measure: Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score Time: Baseline, Study Completion (up to 3 years)PF-06427878 is a new compound proposed for the treatment of hyperlipidemia. The primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of multiple oral doses of PF-06427878 in healthy adult subjects.
Maximum Observed Plasma Concentration (Cmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1. null. --- Q12H ---
Maximum Observed Plasma Concentration (Cmax) for PF-06427878during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12. null. --- Q12H ---
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1. null. --- Q12H ---
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12. null. --- Q12H ---
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 1. null. --- Q12H ---
Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 12. null. --- Q12H ---
Area Under the Curve for PF-06427878 during the dosing interval (AUCtau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Plasma Decay Half-Life (t1/2) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Apparent Volume of Distribution (Vz/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Apparent Oral Clearance (CL/F) of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Minimum Observed Plasma Concentration (Cmin) for PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Peak:Trough ratio of PF-06427878 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Accumulation ratio for Maximum Observed Plasma Concentration (Rac(Cmax)) for PF-06427878 on day14 relative to day 1 during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD. --- Q12H ---
Amount of PF-06427878 excreted in urine (Ae) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Percent of dose excreted in urine as PF-06427878 (Ae%) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Renal clearance of PF-06427878 (CLr) during the dosing interval (tau), ie, 0-8H for Q8H, 0-12H for Q12H, and 0-24H for QD, on day 14. --- Q12H ---
Broad Objectives: To determine the comparative efficacy of commonly employed strategies to overcome loop diuretic resistance when added to concomitant loop diuretics in hospitalized decompensated heart failure patients with hypervolemia Specific Aims: 1. Compare the 48-hour weight change of either intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in decompensated heart failure 2. Compare the adverse effects of electrolyte depletion and renal function changes between intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure 3. Pharmacoeconomic analysis of the direct costs of intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure The investigators will conduct a dual center, randomized, double-blind, double-dummy, parallel design trial comparing: oral metolazone, intravenous chlorothiazide, or oral tolvaptan, in combination with loop diuretics in 60 patients hospitalized for hypervolemic decompensated heart failure and displaying loop diuretic resistance.
Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H ---
Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H ---
Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H --- --- Q12H ---
Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H --- --- Q12H --- --- Q12H ---
Description: The primary outcome will be 48-hour standing scale weight change (kg) from enrollment among the metolazone, intravenous chlorothiazide, and tolvaptan arms, using metolazone group as the comparator group for all other groups.
Measure: Weight change Time: 48 hoursDescription: Net urine output from enrollment to the end of study at 48 hours measured in milliliters and collected either by a foley catheter or via a urine collection cup.
Measure: Net Urine Output Time: 48 hoursDescription: Mean change in serum creatinine (mg/dl) from enrollment to end of study at 48 hours
Measure: Mean Change in Serum Creatinine Time: 48 hoursDescription: Mean change in serum creatinine (mg/dl) from enrollment to end of study at hospital discharge, an average of 5 days
Measure: Mean Change in Serum Creatinine at discharge Time: hospital discharge an average of 5 daysDescription: Mean change in serum potassium (mEq/L) from enrollment to end of study at 48 hours
Measure: Mean Change in Serum Potassium Time: 48 hoursDescription: Cumulative dose of potassium supplementation (mEq) administered from enrollment to end of study at 48 hours
Measure: Potassium Supplementation Time: 48 hoursDescription: Incidence of severe hypokalemia (serum potassium less than 3.0mEq/L ) from enrollment to end of study
Measure: Severe Hypokalemia Time: 48 hoursDescription: Provider escalation of loop diuretic dosage at 24 hours
Measure: Escalation of Loop diuretic therapy Time: 24 hoursDescription: Incidence of new atrial or ventricular arrhythmias from enrollment to end of study at 48 hours
Measure: Cardiac Arrhythmias Time: 48 hoursDescription: pharmacoeconomic analysis of the direct costs in U.S. dollars in each arm for the cost of: study medication. All medication and therapy costs will be defined as the Redbook average wholesale price at the time of the trial to reduce inter-institutional price differences and improve external validity of the analysis.
Measure: Pharmacoeconomic analysis: study drugs Time: 48 hoursDescription: pharmacoeconomic analysis of the direct costs in U.S. dollars in each arm for the cost of additional non-trial protocol laboratory analysis cost related to monitoring of electrolytes
Measure: Pharmacoeconomic analysis: laboratory monitoring Time: 48 hoursDescription: pharmacoeconomic analysis of the direct costs in U.S. dollars in each arm for the cost of addition of additional therapies for suboptimal diuresis (inotropic therapy, vasodilators)
Measure: Pharmacoeconomic analysis: additional therapies Time: 48 hoursDescription: Mean change in serum sodium (mEq/L) from enrollment to end of study at 48 hours
Measure: Mean change in serum sodium Time: 48 hoursDescription: Incidence of death from study enrollment to hospital discharge, an average of 5 days
Measure: In-hospital mortality Time: Enrollment to hospital discharge an average of 5 daysDescription: Incidence of use of dopamine, dobutamine, or milrinone from enrollment to end of study at 48 hours
Measure: Inotrope utilization Time: 48 hoursDescription: Incidence of Renal replacement therapy utilization (hemodialysis, ultrafiltration) from enrollment to hospital discharge, an average of 5 days
Measure: Renal replacement therapy utilization Time: enrollment to hospital discharge an average of 5 daysDescription: Diuretic Efficiency is calculated as 48hr urine output/ 48hr Furosemide equivalents in milligrams
Measure: Diuretic Efficiency Time: 48 hoursDescription: Incidence of hypotension (defined as a systolic blood pressure less than 85mmHg for 2 repeated measurements within 30 minutes or lasting at least 30 minutes or symptomatic hypotension necessitating clinical intervention) from enrollment to 48 hours end of study
Measure: Hypotension Time: 48 hoursDescription: Participants will score their congestion on a 10 point scale ranging from "Best" to "Worst"
Measure: Patient Congestion score Time: at enrollment, at 24 hours, and at 48 hoursThis study is to evaluate the efficacy and safety of a titration method by selects 10 mg control-released (CR) oxycodone tablet as background drug in combined with immediate-released (IR) oxycodone, compared to conventional titration method with immediate-released (IR) oxycodone in patients with moderate to severe cancer pain in Taiwan.
Meanwhile, the titration with IR oxycodone will be added according to the pain intensity, e.g. if patient receiving 6 tablets of 10 mg CR oxycodone (giving in Q12H frequency for 3 days), 12 capsules of 5mg IR oxycodone will be dispensed for managing acute pain (rescue use) for the first cycle. --- Q12H ---
Description: The change from baseline of NRS pain score and the daily number of breakthrough pain
Measure: To evaluate the variable change of NRS pain score and the number of breakthrough pain to obtain pain control after treatment Time: Up to 14 daysDescription: The percentage of patients in each titration cycle
Measure: To evaluate the percentage of patients in each titration cycle Time: Up to 14 daysDescription: The number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control
Measure: To evaluate the number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control Time: Up to 14 daysDescription: The total opioid taken within 24 hrs daily from baseline to day 14
Measure: The total opioid taken within 24hrs daily from baseline to day 14 Time: Up to 14 daysDescription: Mean daily NRS score of patients from baseline to day 14
Measure: To evaluate the mean daily NRS score of subjects from baseline to day 14 Time: Up to 14 daysDescription: The total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14
Measure: To evaluate the total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14 Time: Up to 14 daysDescription: The occurrence rate of adverse events and physical examination status
Measure: To evaluate the tolerability and safety of Oxycodone CR and IR in cancer pain patient Time: Up to 28 daysDescription: The change from baseline in questionnaire
Measure: To evaluate the change from baseline in questionnaire Time: Up to 14 days