I have reported previously on the use of heparinin Ulcerative Colitis. A trial of heparin versus placebo wasrecently done. The study was organized by Dr. Korzenik, now at WashingtonUniversity School of Medicine in St. Louis, MO. I ran one of thesites that participated in the study. The results of the study wereeagerly awaited. The results of the trial were recently reportedat a session of Digestive Disease Week, a major international meeting thatI attended in Orlando, Florida. Following is the abstract as published,with notes afterwards that I added. The short answer is that it works. Read on for details.
AGA Research Forum G3264 #3046
A multi-center, Randomized, Controlled Trial of Heparin for the Treatmentof Ulcerative Colitis
J R Korzenik, Washington Univ Sch of Medicine, St. Louis, MO; MarieE Robert, Yale Univ Sch of Medicine; Alain Bitton, Royal Victoria Hosp;Malcom Robinson, Oklahoma Fdn for Digest Res; Ellen J Scherl, Royal VictorianHosp; Rosemarie L Fisher, Henry J Binder, Yale Univ Sch of Medicine
Background: A series of open-labeled trials suggest a benefit of heparinfor the treatment of Inflammatory Bowel Disease (IBD). No prospective randomizedcontrolled trials have been performed. We report the initial data obtainedfrom a large multicenter controlled trial of heparin therapy for the treatmentof moderate to sever ulcerative colitis (UC). Aims: To assess safety andefficacy of heparin in the treatment of active UC. Methods: Subjects wereenrolled with moderate to severe ulcerative colitis having four or morestools/day. Permissible concomitant medications included mesalamine, steroidsand azathioprine/6-MP for specified durations prior to enrollment. Subjectswere randomized (1:1) to saline injections or standard porcine heparininjections at 10,000 units subcutaneously (sq) bid for 6 weeks. In thoserandomized to heparin, the dose was adjusted by an unblinded observer to10,000 units sq tid for patients whose appt remained below the upper limitof normal. A subgroup (20%) of subjects randomized to placebo receivedtid saline injections. Randomization was stratified by extent of colitis(left sided vs pan - colitis) and by use of steroids. Patients were monitoredwith weekly aPTT and twice weekly CBC. Efficacy was determined by clinicalassessment of stool frequency, frequency of bloody stools, patient globalscale, physician global scale, sigmoidoscopic and histologic assessment(at week 0 and end of week 6). Failure was established by an increase inexisting medications or need for additional medication. Decrease of hematocritby 6 points or decrease of platelets below 100,000 was also criteria fordiscontinuation. Results: 70 subjects were enrolled at 9 sites. No severeadverse effects were observed in any subject. One subject was prematurelydiscontinued because of a decrease in hct of > 6 points but was in remissionat the time with no evidence of bleeding. Three patients noted a transientincrease in rectal bleeding though not clinically significant and wereable to continue their involvement. One patient developed a psoriasiformrash at the injection sites. Enrollment has been completed, but the trialhas not yet been unblinded. Conclusions: 1) The use of heparin is safein the setting of moderate to severe ulcerative colitis. 2) Several subjectsare completing their involvement at this time. Data for clinical efficacywill be reported after the trial is unblinded and will be available shortly.
At the conference the results were further detailed. The majorresult was that the remission rate was 42% for patients on heparin, 20%for control patients. It should be noted that these patients wereall not responding to regular therapy, so heparin was started only latein the course of their UC flare. There was no significant increasein bleeding rates. Patients that did respond all started to respondby three weeks. One issue that was discussed was that the heparinwas given subcutaneously rather than intravaneously. This was donebecause it was an outpatient study. Since heparin given subcutaneouslymay make different fractions of the heparin available differentially, itis possible that IV use is more effective. Note, also, the placeboresponse rate. 20% is somewhat low for a placebo response rate, showingthat these were chronically ill patients. Nonetheless, 20% of patientsdid go into remission with just another month of their treatment withoutheparin. This shows the importance of a placebo controlled trial. Had the control group not been included a result of just 40% response mighthave been believed to be placebo alone. The placebo group shows thatthe response was real.
The information here is from an oral presentation. These resultshave not been published in a journal and have not been carefully reviewedby outside experts. A number of the results described in preliminaryform do not turn out to be true. The usefullness of a preliminaryreport is for early distribution of results and for feedback to the authorbefore publication. Due care needs to be exercised when acting onpreliminary results.
Stephen Holland, M.D.
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