Comparison of famotidine 40 mg with ranitidine 300 mg at night in short-term duodenal ulcer healing. A South African multicentre study

One hundred and thirty-two patients with endoscopically confirmed duodenal ulcers were entered into a 4-6-week double-blind trial of famotidine (Fm) and ranitidine (Rn). Seventy patients were randomised to Fm 40 mg at night and Rn placebo and 62 to Rn 300 mg at night and Fm placebo. Gelusil tablets were allowed for ulcer pain, and diary cards were issued. Clinical evaluations were carried out on entry and at 2 and 4 weeks, and endoscopy was repeated at 4 weeks. Patients with an unhealed ulcer at 4 weeks were continued on the same treatment for another 2 weeks and further endoscopy was carried out at 6 weeks. The groups were comparable with respect to age, sex, duration of the most recent attack, initial ulcer size and smoking, but the duration of disease tended to be longer in the Rn-treated group (P less than 0.05). Of the patients available for analysis, 75% of the Fm-treated and 78% of the Rn-treated patients were healed at 4 weeks and 91% of patients in both treatment groups were healed at 6 weeks. Gelusil consumption and symptomatic responses were comparable in the two groups, and no side-effects were noted apart from mild dizziness in 1 patient after a single Fm tablet. The mean initial size of ulcers healed at 4 weeks was significantly less than that of ulcers which were unhealed at 4 weeks (P less than 0.01), and the healing rate among smokers was significantly lower than that among non-smokers--48 of 72 patients (67%) and 41 of 45 (91%) respectively (P less than 0.01). The study shows that Fm 40 mg at night is as effective as Rn 300 mg in duodenal ulcer healing.     

A comparative study of misoprostol and ranitidine in the healing of duodenal ulcers. A double-blind controlled trial

This study was undertaken to evaluate the safety and therapeutic efficacy of the prostaglandin E1 analogue, misoprostol, when compared with ranitidine in the healing of duodenal ulcers. Sixty patients with endoscopically proven duodenal ulcers participated in a double-blind controlled randomised trial comparing misoprostol 400 microgram and ranitidine 150 mg, both given twice daily orally for up to 8 weeks. Patient characteristics at entry into the trial were similar in the two treatment groups, except that there were 6 women in the ranitidine-treated group and none in the misoprostol-treated group. Ulcers were 0.3 - 2.0 cm in length. Healing was determined by endoscopy at 4 weeks; if ulcers were not healed, endoscopy was repeated at 8 weeks. All patients were given antacid tablets to be used as needed for pain up to a maximum of 8 tablets per day. Healing rates at 4 weeks for a total of 58 evaluate patients in the two treatment groups were: misoprostol (15/29; 51.7%) and ranitidine (20/29; 69.0%). Healing rates at 8 weeks for a total of 55 evaluable patients in the two treatment groups were: misoprostol (21/27; 77.8%) and ranitidine (24/28; 85.7%). The healing rate for misoprostol did not differ significantly from that for ranitidine at both the 4-week (P = 0.28) and the 8-week assessment (P = 0.68). Diarrhoea was the most common side-effect but was usually mild. It occurred in 11 patients on misoprostol and 1 patient on ranitidine. These results indicate that misoprostol 400 micrograms was taken twice daily orally for up to 8 weeks is effective and safe for the treatment of duodenal ulcer.     

Ranitidine heals duodenal ulcers

A double-blind placebo-controlled study of ranitidine 150 mg given twice daily for 4 weeks was carried out in 80 ambulant patients with endoscopically proven duodenal ulceration. Fifteen patients were withdrawn because of poor compliance or default. Of the remaining 65 patients, endoscopic healing (with or without residual erosion) was noted in 28 of the 34 ranitidine-treated patients (82%) and in 14 of the 31 placebo-treated patients (45%) (P less than 0.005). Twenty-three patients whose ulcers were unhealed after 4 weeks of ranitidine therapy or placebo were then given ranitidine for a further 4-week period. Four of these patients were withdrawn, but ulcer healing was achieved in 16 of the remaining 19 patients (4 out of 5 (80%) initially treated with ranitidine and 12 of 14 (86%) initially treated with placebo). No significant clinical, biochemical or haematological adverse reactions were noted in either treatment group. It is concluded that ranitidine is a safe and effective therapy in patients with duodenal ulceration and that initial unsuccessful treatment with placebo does not appear to influence the subsequent response to ranitidine.     

Effect of cimetidine on healing and surgical treatment of gastric ulcers

In this retrospective study, a cohort of gastric ulcer patients treated with antacids was compared with a well-matched group of patients treated with a combination of antacids and cimetidine. Cimetidine combined with antacids enhanced gastric ulcer healing, thereby significantly reducing the number of gastric ulcer operations. Cimetidine appears to act by providing a less acidic environment in which gastric ulcers can heal. The exact mechanism of cimetidine's action on gastric ulcers is not clear. Nonprophylactic administration of cimetidine apparently has no effect on the recurrence rate of gastric ulcers.     

A comparison of 4-week peptic ulcer healing rates following treatment with antacids and ranitidine

Eighty-eight patients with endoscopically proven gastric and duodenal ulceration were treated with ranitidine ( Zantac ; Glaxo) or an antacid preparation containing aluminium hydroxide and magnesium trisilicate ( Gelusil ; Warner) over a 4-week period to assess healing. Clinical, haematological and biochemical assessment and endoscopy were performed at the beginning and at the end of this period. Of the duodenal ulcers, 74% healed on ranitidine therapy and 63% on Gelusil . This difference was not statistically significant (chi 2(1) = 0,55). Of the gastric ulcers 58% healed on ranitidine therapy and 35% on Gelusil , but this difference did not reach statistical significance (chi 2(1) = 1,79). There was no significant difference between the two therapies with regard to symptomatic relief in the duodenal ulcer group, but ranitidine produced significantly better results in the gastric ulcer group. No side-effects were noted in either group.     

Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective,randomised, multicentre study

This 12‐week, prospective, randomised, controlled multi‐centre study compared the proportion of healed diabetic foot ulcers and mean healing time between patients receiving acellular matrix (AM) (study group) and standard of care (control group) therapies. Eighty‐six patients were randomised into study (47 patients) and control (39 patients) groups. No significant differences in demographics or pre‐treatment ulcer data were calculated. Complete healing and mean healing time were 69·6% and 5·7 weeks, respectively, for the study group and 46·2% and 6·8 weeks, respectively, for the control group. The proportion of healed ulcers between the groups was statistically significant (P = 0·0289), with odds of healing in the study group 2·7 times higher than in the control group. Kaplan–Meier survivorship analysis for time to complete healing at 12 weeks showed a significantly higher non healing rate (P = 0·015) for the control group (53·9%) compared with the study group (30·4%). After adjusting for ulcer size at presentation, which was a statistically significant covariate (P = 0·0194), a statistically significant difference in non healing rate between groups was calculated (P = 0·0233), with odds of healing 2·0 times higher in the study versus control group. This study supports the use of single‐application AM therapy as an effective treatment of diabetic, neuropathic ulcers.     

A stable prostacyclin analogue (iloprost) in the treatment of ischaemic ulcers of the lower limb. A Scandinavian-Polish placebo controlled, randomised multicenter study.

The clinical efficacy of the prostacyclin analogue iloprost was studied during a 2 week treatment and 6 month follow-up period in 103 patients with ischaemic ulcers who were randomised to receive active treatment or placebo. Responders were defined as those patients who achieved healing of at least one third of the ulcer area during the study period. The overall responder rate was 41.3%, compared with 25% for the control group (P = 0.086). Side effects including flushing and headache, were common. The study population had a mortality of 23% during the 6 month period, the amputation rate was 43.5% for iloprost and 50% for placebo treated patients. In this severely diseased population of patients a treatment period limited to 2 weeks did not sufficiently improve ulcer healing.     

Two-step autologous grafting using HYAFF scaffolds in treating difficult diabetic foot ulcers: results of a multicenter, randomized controlled clinical trial with long-term follow-up

This study evaluated the efficacy and tolerability of an autologous tissue-engineered graft--a 2-step HYAFF autograft--in the treatment of diabetic foot ulcers compared with standard care. In all, 180 patients with dorsal or plantar diabetic foot ulcers (unhealed for ≥1 month) were randomized to receive Hyalograft-3D autograft first and then Laserskin autograft after 2 weeks (n = 90; treatment group) or nonadherent paraffin gauze (n = 90; control group). Efficacy and adverse events were assessed weekly for 12 weeks, at 20 weeks, and at 18 months. The primary efficacy outcome was complete ulcer healing at 12 weeks. Wound debridement, adequate pressure relief, and infection control were provided to both groups. At 12 weeks, complete ulcer healing was similar in both groups (24% of treated vs 21% controls). A 50% reduction in ulcer area was achieved significantly faster in the treatment group (mean 40 vs 50 days; P = .018). Weekly percentage ulcer reduction was consistently higher in the treatment group. At 20 weeks, ulcer healing was achieved in 50% of the treated group as compared with 43% of controls. Dorsal ulcers had a 2.17-fold better chance of wound healing per unit time following autograft treatment (P = .047). In a subgroup with hard-to-heal ulcers, there was a 3.65-fold better chance of wound healing following autograft treatment of dorsal ulcers (P = .035). Adverse events were similar in both groups. The study results demonstrated the potential of this bioengineered substitutes to manage hard-to-heal dorsal foot ulcers.     

Management of recurrent duodenal ulcer disease

The purpose of this project was to evaluate the medical and surgical treatment of patients with recurrent peptic ulcer disease and to determine whether the addition of cimetidine has altered the treatment outcome. The authors studied 42 patients with recurrent ulcers after duodenal ulcer surgery. Four patients underwent emergency operation for ulcer-related complications, while 38 patients received medical therapy including cimetidine as initial treatment. Medical therapy achieved good results in 18 of 38 patients (47%). The remaining 20 patients either were treated surgically (14) or are still symptomatic. Four of the 18 patients managed operatively had a second recurrent ulcer (22%). There were no deaths. Thirty-two of the original 42 patients (76%) were helped by the treatment. It was concluded that cimetidine has improved medical therapy compared with historical controls but that operative treatment is indicated in about one-half of patients with recurrent peptic ulcer disease.     

Allogeneic keratinocyte for intractable chronic diabetic foot ulcers: A prospective observational study

Chronic diabetic foot ulcers (DFUs) are a common problem in patients with diabetes and are often difficult to treat. The application of newly developed dressing material in patients with chronic DFUs has been reported to be effective. The purpose of this study was to evaluate the usefulness of allogeneic keratinocyte treatment for chronic DFUs. We performed weekly allogeneic keratinocyte treatment for up to 12 weeks in 71 patients with intractable DFUs. We investigated healing rate, wound‐healing velocity, and time to 50% wound size reduction and analysed factors affecting ulcer healing. Fifty‐six patients (78.8%) had complete wound healing. Forty‐six patients (64.7%) showed complete healing within an average of 6.1 weeks, and 10 patients (14.1%) showed partial healing with an average 35.5% reduction vs initial size at the end of follow up. The 10 patients who showed partial healing continued to receive treatment after the 12‐week study period. The mean time to complete wound healing was 7.8 weeks. Fifteen patients (21.1%) experienced treatment failure because of infection, local necrosis, no change in ulcer size, or osteomyelitis during the follow‐up period. No adverse events were observed. Allogeneic keratinocyte treatment is effective for chronic, difficult‐to‐treat DFUs.     

MEASUREMENT OF THE HEALING OF VENOUS ULCERS

The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r= 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments.     

The use of a portable, wearable form of pulsed radio frequency electromagnetic energy device for the healing of recalcitrant ulcers: a case report

Pulsed radio frequency energy (PRFE) has successfully been used to treat diabetic and venous stasis ulcers. In this case report, a lightweight wearable form of a PFRE device was evaluated and used to treat three diabetic foot ulcers and one venous stasis ulcer. The ulcers were present on the four patients for more than 3 months and had failed to heal after conventional treatment. A lightweight battery-powered, wearable form of PRFE device was introduced as a treatment and used 6-8 hours per day for a period of 6 weeks. All patients after 1 week of therapy showed improvement and wound size was seen to decrease. Patient 1 had a venous stasis ulcer, and reported significant pain relief after 2 weeks treatment. Patients 2 and 3 achieved complete healing after 3 weeks treatment, and patients 1 and 4 had a 95% and 88% reduction in wound size, respectively, after the 6-week study period. Both these patients continued to complete healing using the PRFE device after the 6-week study period. PRFE treatment delivered in the form of a wearable lightweight patch appears to offer promise in the treatment of recalcitrant chronic wounds.     

Cimetidine versus surgery for recurrent ulcer after gastric surgery.

The efficacy of cimetidine vs. surgery in the treatment of recurrent ulcers after definitive surgery for chronic duodenal ulcer was evaluated in two comparable groups (23 each) of patients. Cimetidine 1 g daily healed 79% and 91.6% of recurrent ulcers, as assessed endoscopically, after 6 and 12 weeks respectively. At the end of one year, maintenance treatment with cimetidine (400 mg nocte) prevented relapse in 89.5% of the healed ulcers, while surgery was successful in 94.4% (p greater than 0.1). The cimetidine group experienced significantly (p less than 0.05) less side effects than the surgical group, with respectively 10% and 50% of patients having Visick grade II and above. After one year of maintenance treatment, cimetidine was withdrawn, and ulcer recurred in 71.4% within six months. The relapse rates between the two groups were significantly different by life-table analysis (p less than 0.01). We conclude that cimetidine was as effective as surgery in preventing relapse of postsurgical recurrent ulcers and had fewer side effects, but indefinitely prolonged therapy appeared necessary.     

Comparison of the efficacy of 4- and 8-week lansoprazole treatment for ESD-induced gastric ulcers: a randomized, prospective, controlled study

Background

Although endoscopic submucosal dissection (ESD) is widely used to treat gastric neoplasms, there is no consensus for the optimal treatment for ESD-induced ulcers. We compared efficacy between 4 and 8 weeks of lansoprazole treatment for iatrogenic gastric ulcers that developed after ESD.

Methods

Eighty-four patients who were diagnosed with gastric adenoma or early gastric cancer were enrolled and randomly assigned to treatment with lansoprazole (30 mg/day) for 4 or 8 weeks. Eight weeks after ESD, we conducted follow-up endoscopy to compare ulcer stage and ulcer reduction ratio (dividing the ulcer dimension at 8 weeks by the initial ulcer dimension) between the two groups.

Results

From the 84 patients, 69 patients were included in the final analysis, with 34 in the 4-week group and 35 in the 8-week group. Eight weeks after ESD, there were no significant difference observed between the two groups in terms of the ulcer stage (68 % in the scar stage in the 4-week group vs. 69 % in the 8-week group, P = 0.93) or the ulcer reduction ratio (0.0081 ± 0.015 in the 4-week group vs. 0.0037 ± 0.008 in the 8-week group, P = 0.15). Also, in the subgroup analysis among the patients with large ulcers (>30 mm), those parameters were not different.

Conclusions

For ESD-induced gastric ulcers, treatment with lansoprazole for 4 weeks was as effective as treatment for 8 weeks. Considering cost-effectiveness, proton pump inhibitor therapy for 4 weeks may be sufficient for ESD-induced gastric ulcers.     

Measurement of the healing of venous ulcers.

The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r = 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments.     

Autologous platelet‐rich fibrin matrix as cell therapy in the healing of chronic lower‐extremity ulcers

A novel autologous platelet‐rich fibrin matrix membrane (PRFM) was assessed for the ability to facilitate healing in patients with chronic lower‐extremity ulcers. Preliminary data are presented from a prospective trial (n=21). Twelve patients were identified with 17 venous leg ulcers (VLU) and nine bearing 13 nonvenous lower‐extremity ulcers. Before enrollment, the patients were evaluated for vascular status and received appropriate surgical intervention to optimize arterial and venous circulatory status. None of the ulcers had responded to a variety of standard treatments from 4 months to 53 years. Initial ulcer size ranged from 0.7 to 65 cm² (mean, 11.2 cm²). Each PRFM‐treated patient received up to three applications of either a 35 or 50 mm fenestrated membrane, depending on initial ulcer size. The primary endpoints were percent and rate of complete closure as measured by digital photography, computerized planimetery, and clinical examination. Patients were followed weekly for 12 weeks with a follow‐up visit at 16 weeks. At each 4‐week interval, the extent of healing was assessed, and those patients with >50% reduction in wound area were allowed to continue to complete closure. Patients with <50% closure received repeated applications. Complete closure was achieved in 66.7% of the VLU patients (64.7% of treated ulcers) in 7.1 weeks (median, 6 weeks) with an average of two applications per patient. Forty‐four percent complete closure was seen with non‐VLU patients (31% of treated ulcers). From the results of this small‐scale pilot study, PRFM shows significant potential for closing of chronic leg ulcers.     

Healing rates and cost efficacy of outpatient compression treatment for leg ulcers associated with venous insufficiency.

OBJECTIVE: Although newer techniques to promote the healing of leg ulcers associated with chronic venous insufficiency are promising, improved healing rates and cost effectiveness are unproven. We prospectively followed a series of patients who underwent treatment with outpatient compression for venous stasis ulcers without adjuvant techniques to determine healing rates and costs of treatment. METHODS: Two hundred fifty-two patients with clinical or duplex scan evidence of chronic venous insufficiency and active leg ulcers underwent treatment with ambulatory compression techniques. The patients were prospectively followed with wound measurements at 1-week to 2-week intervals, and the factors that were associated with delayed healing were determined. RESULTS: Of all the ulcers, 57% were healed at 10 weeks of treatment and 75% were healed at 16 weeks. Ultimately, 96% of the ulcers healed, and only 1 major amputation was necessitated (0.4%). Initial ulcer size and moderate arterial insufficiency (ankle brachial index, 0.5 to 0.8; n = 34) were factors that were independently associated with delayed healing (P <.01). Patient age, ulcer duration before treatment, and morbid obesity did not significantly affect healing times. The cost of 10 weeks of outpatient treatment with compression techniques ranged from $1444 to $2711. CONCLUSION: The treatment of venous stasis ulcers with compression techniques results in reliable, cost-effective healing in most patients. Current adjuvant techniques may prove to be useful but are likely to be cost effective only in a minority of cases, particularly in patients with large initial ulcer size or arterial insufficiency.     

Randomized, prospective trial of cimetidine and ranitidine for control of intragastric pH in the critically ill

Forty-eight critically ill patients in an intensive care unit were enrolled in a prospective study of stress ulcer prophylaxis. The H2-receptor antagonists cimetidine and ranitidine were used, patients being randomized on hospital number. Response was assessed by measuring gastric pH every 2 hours. The drugs were administered by intravenous infusion, and up to three dosage increments fo each of the drugs were titrated against the pH of the aspirated gastric juice. If one drug, in maximum dose, failed to maintain the pH above 4, the other drug was administered at maximum dose. If both drugs failed to achieve control of gastric pH, antacids were administered in an endeavor to ensure patient safety. Cimetidine was successful in maintaining the intragastric pH above 4, for the duration of the intensive care admission, in five of 28 patients. Ranitidine was successful in 10 of 20 patients. The difference between these two groups was statistically significant (p = 0.04). In patients in whom cimetidine therapy failed, ranitidine provided adequate control of pH in four of 13. Cimetidine controlled one of six patients who had failed to improve with ranitidine therapy. Plasma concentrations of both drugs were well above established acid inhibitory concentrations. However, even with much lower plasma concentrations of ranitidine, similar amounts of both drugs were present in the gastric juice, suggesting a possible explanation for the greater efficacy of ranitidine. We conclude that, although ranitidine is more effective than cimetidine, neither of these drugs is adequate for stress ulcer prophylaxis. If they ae used for this purpose in the critically ill patient, regular monitoring of gastric pH is essential to allow detection of therapeutic failures.     

Bicitropeptide, antacid and placebo in gastric and duodenal ulceration. A two-centre, double-blind, comparative endoscopic study.

A bismuth-peptide complex (BCP Compound), an antacid (Maalox) and corresponding placebos were studied in a 6-week comparative double-blind trial of treatment in 106 randomized ambulant patients with endoscopically proven duodenal and gastric ulcers. Patients were examined after 1, 3 and 6 weeks' treatment and results assessed separately for duodenal and gastric ulcers on endoscopic evidence at weeks 3 and 6 respectively. Bicitropeptide was significantly better than antacid and placebo at 3 and 6 weeks for treatment of both duodenal and gastric ulcers. In the bicitropeptide group 100% of the patients in the duodenal ulcer group and 95,2% in the gastric ulcer group responded to treatment (improved or healed). No haematological or biochemical changes were noted and no adverse effects were recorded.     

A prospective,multicentre, randomised controlled study of human fibroblast‐derived dermal substitute (Dermagraft) in patients with venous leg ulcers

This was an open‐label, prospective, multicentre, randomised controlled study to evaluate the efficacy and safety of human fibroblast‐derived dermal substitute (HFDS) plus four‐layer compression therapy compared with compression therapy alone in the treatment of venous leg ulcers. The primary outcome variable was the proportion of patients with completely healed study ulcers by 12 weeks. The number healed was further summarised by ulcer duration and baseline ulcer size. Sixty‐four (34%) of 186 patients in the HFDS group experienced healing by week 12 compared with 56 (31%) of 180 patients in the control group (P = 0·235). For ulcers ≤ 12 months duration, 49 (52%) of 94 patients in the HFDS group versus 36 (37%) of 97 patients in the control group healed at 12 weeks (P = 0·029). For ulcers ≤ 10 cm², complete healing at week 12 was observed in 55 (47%) of 117 patients in the HFDS group compared with 47 (39%) of 120 patients in the control group (P = 0·223). The most common adverse events (AEs) were wound infection, cellulitis and skin ulcer. The frequency of AEs did not markedly differ between the treatment and control groups.