Mark Vb Cleveland

A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation.

OBJECTIVES:Polyethylene glycol (PEG) 3350 (MiraLAX) is currently approved for the short-term treatment of occasional constipation. This study was designed to compare the safety and efficacy of PEG laxative versus placebo over a 6-month treatment period in patients with chronic constipation.METHODS:Study subjects who met defined criteria for chronic constipation were randomized in this double-blind, placebo-controlled, parallel, multicenter study to receive PEG laxative as a single daily dose of 17 g or placebo for 6 months. Baseline constipation status was confirmed during a 14-day observation period. As a primary efficacy variable, treatment success was defined as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were assessed. An Interactive Voice Response System (IVRS) recorded daily bowel movement experience and study efficacy and safety information. Laboratory testing at baseline and monthly for the study duration was analyzed for hematology, blood chemistry including amylase, GGT, uric acid, lipids, and urinalysis.RESULTS:A total of 304 patients were enrolled and received treatment at one of 50 centers. Successful treatment according to the primary efficacy variable was seen in 52.0% of PEG and 11% of placebo subjects (P < 0.001). Similar efficacy was seen in a subgroup of 75 elderly subjects. According to the primary efficacy definition (based on individual treatment weeks), 61% of PEG treatment weeks versus 22% of the placebo weeks were successful (P < 0.001). There were no significant differences in laboratory findings or adverse events except for the gastrointestinal category where diarrhea, flatulence, and nausea were the most frequent with PEG although they were not individually statistically significant compared with placebo. Similar results were observed when analyzed for differences due to gender, race, or age.CONCLUSIONS:PEG laxative is safe and effective for use in patients with chronic constipation for 6 months.

Comparison of reduced volume versus four liters sulfate-free electrolyte lavage solutions for colonoscopy colon cleansing

OBJECTIVE: In an attempt to improve patient tolerance for colonoscopy cleansing, a reduced volume lavage regimen with 2 L sulfate-free electrolyte lavage solution (SF-ELS, NuLYTELY, Braintree Laboratories, Braintree, MA) plus 20 mg p.o. bisacodyl (Half Lytely, Braintree Laboratories) was compared with standard 4 L SF-ELS lavage for safety and efficacy. METHODS: At two centers, 200 patients undergoing colonoscopy for routine indications were randomized to receive the reduced volume or standard 4 L method. The day before scheduled colonoscopy, study subjects were allowed a normal breakfast and clear liquids for lunch and dinner. Those randomized to receive the reduced volume method received four 5-mg bisacodyl tablets p.o. at noon. Six hours later, they received 2 L SF-ELS given as 10 oz every 10 min. Subjects randomized to receive 4 L SF-ELS also drank their solution at 6:00 PM in a similar fashion. Colonoscopists, unaware as to the randomized preparation received, rated efficacy of cleansing. Patient tolerance and various hematological and biochemical parameters were assessed. RESULTS: Physician assessment of colon cleansing showed no differences between those patients randomized to receive reduced volume (n = 93) or 4 L (n = 93) SF-ELS cleansing (p = 0.16). There was a profound reduction in preparation side effects. The reduced volume preparation had less fullness (p < 0.01), nausea (p < 0.01), vomiting (p = 0.01), and overall discomfort (p < 0.01). There were no clinically significant changes in hematology or blood chemistry associated with either preparation. CONCLUSIONS: Reduced volume preparation with 2 L SF-ELS and bisacodyl is safe and effective. Clinical symptoms from the reduced volume preparation are significantly reduced compared with traditional 4 L gut lavage.

A randomized clinical study evaluating the safety and efficacy of a new, reduced-volume, oral sulfate colon-cleansing preparation for colonoscopy.

OBJECTIVES:We sought to evaluate a new, low-volume, oral sulfate solution as a bowel preparation for colonoscopy in adult patients.METHODS:The investigations were designed as two multicenter, single-blind, randomized, non-inferiority studies to show that the sulfate regimen would effect cleansing that is acceptable and equivalent to polyethylene glycol electrolyte solution with ascorbic acid (PEG-EA), and would be suitable for colonoscopy. One study evaluated same-day administration; the other compared the two study preparations given by split-dose administration in which the first portion was taken the evening before colonoscopy and the second portion on the morning of the procedure. The primary efficacy variable was based on bowel cleansing graded by an investigator who was unaware of the preparation method received.RESULTS:Study 1 randomized 408 outpatients scheduled for colonoscopy for routine indications, with 387 subjects taking the preparation. In all, 364 subjects were randomized and took the preparation in study 2. The demographics of the enrolled subjects were similar across both treatment groups in the two studies, including gender, race, and ethnic characteristics. The primary efficacy analysis supports the conclusion that the oral sulfate solution produces the same degree of cleansing as PEG-EA. Successful preparations were seen in 82.4% and 80.3% in study 1 and 97.2% and 95.6% in study 2 for the oral sulfate solution and the PEG-EA regimen, respectively. Although no difference in excellent preparations was seen in the 1-day preparation, split-dose administration resulted in more excellent preparations in the sulfate group than in the PEG-EA group (63.3 vs. 52.5%, P=0.043). Preparation-related symptoms of cramping, bloating, nausea, and vomiting were generally mild and infrequent. Sulfate subjects reported slightly increased gastrointestinal events and higher vomiting scores (P=0.009) in the 1-day preparation but not in the split-dose regimen. There were no other differences for adverse events or clinically significant laboratory findings, including no increased creatinine.CONCLUSIONS:The new 960 -ml oral sulfate solution is effective for colonoscopy cleansing and has an acceptable safety profile.

A low-sodium solution for gastrointestinal lavage

Golytely is a sodium sulfate-based solution used for lavage cleansing of the colon. Although most patients and physicians prefer Golytely lavage over other methods of bowel cleansing, its highly salty taste is a drawback. This report describes the development of a modified lavage solution that has a barely perceptible salty taste. This solution was developed by removing sodium sulfate, increasing the concentration of polyethylene glycol, and making minor adjustments in the concentration of other salts. Golytely, reduced sodium sulfate Golytely (Golytely-RSS), and a balanced electrolyte solution were infused into the stomachs of normal subjects. After steady-state lavage conditions were established, the rates of fluid and electrolyte absorption were measured. Average fluid absorption rate was 791 ml/h with the balanced electrolyte solution, compared with only 63 and 45 ml/h with Golytely and Golytely-RSS, respectively. Golytely-RSS was studied at 3 infusion rates, from 0.9-1.8 L/h, and the time and volume of solution required for colon cleansing was determined; the lower infusion rate (0.9 L/h) took longer but required less solution to cleanse the colon. In conclusion, Golytely-RSS has the essential feature of Golytely; i.e., lavage is associated with negligible salt and water absorption. The less-salty taste of Golytely-RSS may make it less difficult to drink and thereby enhance patient compliance; the total volume of solution required for cleansing is less when the solution is ingested at 0.9 L/h than when the ingestion rate is 1.8 L/h.

Calcium Acetate Control of Serum Phosphorus in Hemodialysis Patients

Calcium acetate has many characteristics of an ideal phosphorus binder. It is a readily soluble salt that avidly binds phosphorus in vitro at pH 5 and above. One-dose/one-meal balance studies show it to be more potent than calcium carbonate or calcium citrate. We studied chronic (3-month) phosphorus binding with calcium acetate in 91 hyperphosphatemic dialysis patients at four different centers. All phosphorus binders were stopped for 2 weeks. Calcium acetate at an initial dose of 8.11 mmol (325 mg Ca2+) per meal was then used as the only phosphorus binder. Dose was adjusted to attempt control of predialysis phosphorus level less than 1.78 mmol/L (5.5 mg/100 mL). Final calcium acetate dose was 14.6 mmol (586 mg) Ca2+ per meal. Sixteen patients developed mild transient hypercalcemia (mean, 2.84 mmol/L [11.4 mg/dL]. Initial phosphorus values in mmol/L (mg/dL) were 2.39 (7.4); at 1 month, 1.91 (5.9); and at 3 months, 1.68 (5.2). Initial calcium values in mmol/L (mg/dL) were 2.22 (8.9); at 1 month, 2.37 (9.5); and at 3 months, 2.42 (9.7). Initial aluminum values in mumol/L (micrograms/L) were 2.99 (80.7); and at 3 months were 2.54 (68.4). Initial C-terminal parathyroid hormone (C-PTH) values in ng/mL were 14.6; at 1 month, 11.9; and at 3 months, 13.2. Sixty-nine patients then entered a double-blind study. Phosphorus binders were stopped for 1 week. Calcium acetate (at a dose established in a prior study) or placebo was then administered for 2 weeks. Next, patients were crossed to the opposite regimen for 2 weeks. Initial phosphorus was 2.36 mmol/L (7.3 mg/100 mL) and calcium 2.22 mmol/L (8.9 mg/100 mL).(ABSTRACT TRUNCATED AT 250 WORDS)

PEG3350 in the Treatment of Childhood Constipation : A Multicenter, Double-Blinded, Placebo-Controlled Trial

OBJECTIVE To establish the efficacy and best starting dose of polyethylene glycol (PEG)3350 in the short-term treatment of children with functional constipation. STUDY DESIGN Prospective, randomized, multicenter, double-blinded, placebo-controlled, dose-ranging study of PEG3350 in children with functional constipation. Patients were randomly assigned to either placebo or 0.2 g/kg per day, 0.4 g/kg per day, or 0.8 g/kg per day of PEG3350 after a 1 week run-in period, followed by 2 weeks of treatment. All received behavior modification. The primary outcome was the proportion of patients with a successful treatment response: >or=3 bowel movements (BM) in the second week. RESULTS 103 children (mean, 8.5 +/- 3.1 years) were enrolled. 77%, 74%, and 73% of the 0.2, 0.4, and 0.8 g/kg groups were successfully treated, as compared with 42% receiving placebo (P < .04). There was a significant increase in BM (P < .001) and straining improvement (P < .05) with the different PEG3350 doses. Stool consistency improved significantly for doses 0.4 g/kg or higher (P < .001). There was more abdominal pain and fecal incontinence in patients receiving 0.8 g/kg. PEG3350 was well tolerated. CONCLUSIONS This placebo-controlled study confirms the efficacy and safety of PEG3350 for the short-term treatment of children with functional constipation. We recommend a starting dose of 0.4 g/kg per day.

A Randomized, Multicenter Comparison of Polyethylene Glycol Laxative and Tegaserod in Treatment of Patients With Chronic Constipation

OBJECTIVE: Polyethylene glycol (PEG) 3350 (MiraLax) and tegaserod (Zelnorm), a serotonin subtype 4 receptor partial agonist, are currently approved for treatment of constipation. This study was designed to compare the efficacy of each product over a 4-wk treatment period.METHODS: Study patients who met defined criteria for chronic constipation were randomized in this open-labeled, parallel, multicenter study to receive the PEG laxative as a single daily dose of 17 g or tegaserod tablets 6 mg b.i.d., for 28 days. As a primary end point, treatment success was defined for each patient as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were also assessed. An interactive voice response system (IVRS) recorded patient reported daily bowel movement experience and study efficacy and safety information.RESULTS: A total of 237 patients were enrolled and received treatment at one of 25 centers. Successful treatment according to the primary end point was seen in 50.0% of the PEG and 30.8% of tegaserod patients (P = 0.003). By treatment weeks 3 and 4, significantly more PEG patients were successfully treated according to primary and secondary response definitions. PEG patients experienced more bowel movements per week (P = 0.019) and had significantly greater improvement in constipation symptoms (P = 0.016) based on results from a validated patient self-reported questionnaire. Tegaserod patients experienced a significantly higher incidence of headaches. Otherwise, there were no significant differences in adverse events.CONCLUSIONS: While PEG laxative and tegaserod are safe for their intended use in chronic constipation, PEG had superior efficacy, caused fewer headaches, and produced greater improvement of constipation symptoms. Trial is registered at: http://www.clintrials.gov. Unique registration number: NCT00153140

A randomized clinical study comparing reduced-volume oral sulfate solution with standard 4-liter sulfate-free electrolyte lavage solution as preparation for colonoscopy.

BACKGROUND Low-volume bowel preparations for colonoscopy improve tolerability. OBJECTIVE We compared the efficacy, tolerability, and safety of a new low-volume sulfate solution with a standard 4-L polyethylene glycol electrolyte lavage solution as bowel preparation for colonoscopy. DESIGN Multicenter, single-blind, randomized, noninferiority study. SETTING Five academic and community endoscopy centers in the United States. PATIENTS One hundred thirty-six outpatients undergoing colonoscopy. INTERVENTIONS Patients were randomized to receive 4 L sulfate-free electrolyte lavage solution (SF-ELS) given the night before colonoscopy versus 12 oz oral sulfate solution (OSS) given in equally divided doses the evening before and the morning of colonoscopy. MAIN OUTCOME MEASUREMENTS Successful (ie, good or excellent) bowel preparation. RESULTS Successful bowel preparation was more frequent with OSS than with SF-ELS (98.4% vs 89.6%; P = .04). Excellent preparation also was achieved more frequently with OSS (71.4% vs 34.3%; P < .001). Patients receiving OSS had less residual stool in the cecum and ascending colon and less residual fluid in the cecum and ascending, transverse, and descending colon compared with SF-ELS. The percentage of patients with GI side effects and adverse events was not significantly different between the 2 groups. LIMITATIONS The OSS was administered in split doses, whereas the SF-ELS was administered the evening before (which is its FDA-approved regimen). CONCLUSIONS Oral sulfate solution is promising as a safe low-volume preparation for colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER NCT00856843.).

Overnight efficacy of polyethylene glycol laxative

OBJECTIVES:Clinical studies in constipated adult patients have shown that a 17- or 34-g daily dose of polyethylene glycol (PEG) 3350 (MiraLax) is safe and effective for the treatment of constipation, with the best efficacy seen in wk 2 of treatment. The purpose of this study was to determine an optimal dose of PEG to provide satisfactory relief of constipation within 24 h.METHODS:A total of 24 adult study subjects who met Rome II criteria for constipation were randomized in a double-blind, parallel pilot study to receive a single dose of placebo or PEG laxative at doses of 51, 68, or 85 g in 500 ml of flavored water. Over a 72-h period, subjects rated bowel movements (BM), completeness of evacuation, and satisfaction.RESULTS:The 68-g dose seemed to be most satisfactory. Five of six subjects had a BM within 24 h. The time to first BM was 14.8 h for 68 g versus 27.3 h for placebo (p = NS). The time to second BM was 19.2 h versus 47.2 h for 68 g and placebo, respectively (p = 0.003). Of the subjects receiving 68 g of PEG, 50% and 100% reported complete evacuation for the first and second BM, respectively. The average number of BMs in 24 h for placebo, 51 g, 68 g, and 84 g were 0.5, 2.2, 2.2, and 4.2, respectively (p = 0.004). There were no adverse reactions, and no patient reported incontinence or complained of cramps or diarrhea at any dose. There were no changes in measured electrolytes, calcium, glucose, BUN, creatinine, or serum osmolality.CONCLUSIONS:A 68-g dose of PEG laxative seems to provide safe and effective relief in constipated adults within a 24-h period.

A comparison of oral sulfate solution with sodium picosulfate: magnesium citrate in split doses as bowel preparation for colonoscopy.

BACKGROUND There are few data comparing U.S. Food and Drug Administration-approved low-volume bowel preparations for colonoscopy. OBJECTIVE To compare oral sulfate solution (OSS) with sodium picosulfate plus magnesium citrate (SP+MC) for bowel cleansing efficacy. DESIGN Single-blind, randomized, controlled trial. SETTING Ten U.S. centers. PATIENTS Outpatients undergoing colonoscopy for routine indications. INTERVENTIONS Patients were randomized to undergo bowel preparation with OSS or SP+MC. Both preparations were given in split doses. MAIN OUTCOME MEASUREMENTS Cleansing efficacy on a 4-point scale from excellent (4) to poor (1). RESULTS Among 338 randomized patients who took preparation, OSS resulted in a higher rate of successful (excellent or good) preparation (94.7% vs 85.7%; P = .006) and more excellent preparations (54% vs 26%; P < .001) compared with SP+MC. There was no difference between OSS and SP+MC in treatment-emergent adverse events. SP+MC had better scores for nausea, but the differences were small. LIMITATIONS The preparation grading scale has been used in previous studies and has regulatory acceptance but has not been formally validated. CONCLUSION The U.S. Food and Drug Administration-approved split-dose regimen of OSS provides superior bowel cleansing compared with the approved split-dose regimen of SP+MC. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01786629.).