***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Iloprost , a stable prostacyclin analogue , was given by intravenous infusion to 29 patients with severe Raynaud 's phenomenon , 26 of whom had systemic sclerosis ( SS ) , and compared with placebo infusion in a double blind crossover trial . Iloprost significantly lessened the number and the severity of attacks compared with placebo . Nine patients expressed a preference for effectiveness of treatment , eight of these in favour of Iloprost .  Thermography failed to show any long term effect of Iloprost . Side effects of headache , flushing , nausea , and vomiting were common , and the inconvenience of intravenous administration may limit its routine use OBJECTIVE --To compare the efficacy , tolerance and safety of 50 - 150 micrograms orally administered iloprost given twice a day versus placebo in patients with Raynaud 's syndrome . METHODS --The study was multicentre ( n = 3 ) , double blind and placebo controlled . Sixty three patients who had eight or more vasospastic attacks per week were enrolled . After a one week run-in period , all patients received either iloprost or placebo treatment to a maximum tolerated dose of 150 micrograms twice a day for 10 days . Diary cards assessed the duration and severity of the vasospastic attacks . Side effects were monitored by direct question ing . A global assessment of treatment efficacy was made by the patient at the end of treatment and two weeks later . RESULTS --Patient opinion tended to favour iloprost at the end of the 10 day treatment phase ( p = 0.09 ) and this was significant at day 24 ( the follow up visit ) ( p = 0.011 ) . Although the duration and severity of attacks tended to decrease in the iloprost treated group , these results tended not to reach statistical significance ( for severity p = 0.06 at end of treatment , p = 0.09 on day 24 ) . CONCLUSION --Iloprost administered intravenously has been shown to be of benefit in the treatment of the Raynaud 's syndrome associated with systemic sclerosis , but this route of administration is inconvenient . This study evaluated the use of iloprost administered orally to patients with Raynaud 's syndrome . Patient documented improvement was significantly improved by iloprost . Diary card analysis showed a trend in favour of iloprost , but these results did not reach statistical significance R and omized controlled trials ( RCTs ) in Raynaud 's phenomenon ( RP ) have shown conflicting efficacy data . Also , there is no consensus on the outcome measures that should be used . Our objectives were to assess the reliability of individual core set measures used in 3 RCTs , evaluate the placebo response for individual core set measures , and determine if a composite of individual core set measures will decrease the placebo response , which may improve our ability to see treatment effects in future trials OBJECTIVE We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud 's phenomenon secondary to systemic sclerosis . METHODS Thirty-five patients with Raynaud 's phenomenon secondary to systemic sclerosis , including 11 with digital ischemic ulcerations , were enrolled in a double blind placebo controlled parallel study in 2 centers . Following a 2 week washout , subjects received intravenous iloprost ( 0.5 - 2.0 ng/kg/min ) or saline by continuous infusion for 6 h on 5 consecutive days . Clinical assessment s , status of digital ulcers , measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge , were performed at entry , at 5 days of therapy and at biweekly intervals for 10 weeks . RESULTS Complete healing of all cutaneous lesions ( ulcers , fissures , and paronychia ) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo ( p = 0.015 ) . Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group , but none in the placebo group ( p = 0.029 ) . Patient diaries of frequency , duration and symptoms of Raynaud 's phenomenon showed improvement in both groups . Critical ischemic temperature ( finger temperature during controlled cold challenge at which Raynaud 's or loss of detectable digital blood flow occurred ) progressively decreased in the iloprost group from 21.3 + /- 7.3 degrees C at baseline to a minimum of 16.1 + /- 3.2 degrees C at 8 weeks after treatment ( p = 0.076 ) , whereas no consistent changes were observed in the placebo group . Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge . No changes were noted in ambient digital skin temperature , total digital blood flow , finger systolic pressure or in measures of in vivo platelet activation . One subject dropped out with chest pain , but adverse effects of nausea , vomiting , headache and jaw pain were otherwise limited to the 5 days of drug infusion . CONCLUSION Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear Twelve female patients with severe secondary Raynaud 's phenomenon were treated in a r and omized order with both placebo and Iloprost infusions . Infusions were for 5 hours on 3 consecutive days and Iloprost was administered at variable dosage from 1.0 to 3.0 ng/kg/min . A 6-week follow-up period was used between the two sets of infusions . A significant number of patients reported Iloprost had improved Raynaud 's symptomatology compared with placebo and this effect lasted for up to 6 weeks . The number of attacks of Raynaud 's as recorded by patients in diary books was similarly reduced after Iloprost .  Digital and nail-bed blood flows measured by laser-Doppler methods were increased for up to 6 weeks after Iloprost , but not after placebo infusions . Iloprost may be a useful therapeutic agent in the treatment of severe secondary Raynaud 's syndrome OBJECTIVE To evaluate the efficacy and tolerability of an oral preparation of iloprost , a prostacyclin analog , in patients with Raynaud 's phenomenon ( RP ) secondary to systemic sclerosis ( scleroderma ) . METHODS A multicenter , r and omized , parallel-group , placebo-controlled double-blind study was performed at university and community-based medical centers . Patients were r and omly assigned to receive either 50 microg of iloprost orally twice daily or an identical gelatin-coated capsule containing placebo for 6 weeks . Outcome measures included average total daily duration of RP attacks , average number of RP attacks , and RP condition scored via a st and ardized daily diary . RESULTS Three hundred eight patients with scleroderma ( 272 women , 36 men , mean age 49 years [ range 18 - 80 ] ) were enrolled . One hundred fifty seven were assigned to receive iloprost and 151 to receive placebo .  One hundred forty-three patients in the iloprost group ( 91.1 % ) and 144 in the placebo group ( 95.4 % ) completed the 6-week treatment phase . Fifteen of these treated patients ( 8 iloprost , 7 placebo ) failed to complete all of the followup visits . The mean reduction in the average duration of attacks from baseline to week 5 - 6 was 24.32 minutes in the iloprost group and 34.34 minutes in the placebo group ( P = 0.569 ) . Likewise , the mean reduction from baseline to week 5 - 6 in the daily frequency of attacks was 1.02 in the iloprost group and 0.83 in the placebo group ( P = 0.459 ) . The Raynaud 's condition score , a patient-completed assessment of the severity of RP attacks , was reduced by 1.32 in the iloprost group and 1.00 in the placebo group ( P = 0.323 ) . The lack of significant difference between treatment groups did not change when a variety of factors , including use of other vasodilators , duration of disease , classification of scleroderma ( limited versus diffuse ) , or number of baseline digital ulcers were taken into account . Premature withdrawal from the study due to adverse events occurred in 10 patients ( 6.4 % ) in the iloprost group and 3 ( 2.0 % ) in the placebo group ( P = 0.058 ) . CONCLUSION Oral iloprost at a dosage of 50 microg twice daily is no better than placebo for management of RP secondary to scleroderma , either during 6 weeks of treatment or during 6 weeks of posttreatment followup Iloprost is a chemically stable analog of prostagl and in I2 showing the same properties as the naturally occurring substance , but with advantages of ease of h and ling and administration to patients . A double blind within patient comparison of intravenous iloprost and placebo was undertaken in 13 patients with Raynaud 's phenomenon severe enough to warrant short term hospitalization for intravenous dilator therapy ; thermography was used as one form of assessment . Our results , while showing improvements in frequency of Raynaud 's attacks after iloprost compared with placebo , show no significant effects on other variables Raynaud phenomenon occurs in more than 90 % of patients with systemic sclerosis . In these patients the digital arteries and precapillary arterioles show marked fibrosis of the intima and luminal narrowing [ 1 , 2 ] . This peripheral vascular disease has been associated with in vivo platelet activation and abnormal vascular reactivity [ 3 - 5 ] . Vasodilator therapy can prevent or ameliorate Raynaud episodes in patients with scleroderma , thus providing increased blood flow and healing of ischemic digital lesions . Unfortunately , currently available vasodilators are incompletely effective in treating Raynaud phenomenon in patients with systemic sclerosis [ 6 , 7 ] . Iloprost is a chemically stable prostacyclin analog with both vasodilating and platelet inhibitory effects [ 8 - 10 ] . Iloprost is not yet available but is being studied in clinical trials for various vascular conditions , including ischemic ulcers , pulmonary hypertension , and vasospastic disorders . Short-term intravenous infusions of prostacyclin have been beneficial in the treatment of Raynaud phenomenon [ 11 - 14 ] . Previous studies suggest that iloprost is helpful in the treatment of Raynaud phenomenon and ischemic ulcers secondary to systemic sclerosis [ 15 - 22 ] . However , these studies have been conducted on small numbers of patients and have either been uncontrolled [ 19 - 21 ] or based on a cross-over design [ 15 - 17 ] . Because the effects of iloprost may persist for 6 to 10 weeks , a parallel study design is preferable . We report the first double-blind , placebo-controlled , parallel-group , multicenter study design ed to investigate the efficacy of iloprost in treating patients with Raynaud phenomenon secondary to systemic sclerosis . Methods Patients Out patients with Raynaud phenomenon secondary to systemic sclerosis with either diffuse cutaneous or limited cutaneous variants from 12 clinical centers were eligible to enter the study . The diagnosis of Raynaud phenomenon was based on a history of  episodic digital pallor and cyanosis .  The diagnosis of systemic sclerosis was made according to the classification criteria developed by the American Rheumatism Association [ 23 ] . Patients were considered to have sufficiently severe Raynaud phenomenon for study entry if they met either of the following criteria : a minimum of 8 Raynaud attacks per week documented by patient diary during the 2 weeks before the first day of infusion or one or more cutaneous ischemic finger lesions ( ulcers , fissures , or paronychiae ) . The patient could be male or female and at least 18 years old . Women of childbearing age were required to practice a medically acceptable method of birth control and to have a negative pregnancy test 1 week before the start of infusion and on the morning of the first day of infusion . All the patients provided written informed consent . Patients were excluded if they met any of the following conditions : surgical sympathectomy done within the past 12 months ; bleeding diathesis or a platelet disorder ; stroke , transient cerebral ischemic attack , or myocardial infa rct ion within the past 6 months ; history of angina pectoris within the preceding 12 months ; evidence within the preceding 4 weeks of the onset of renal disease manifested by new hypertension or abnormal urinalysis results , evidence of microangiopathic hemolytic anemia , or azotemia ; hypertension not controlled by diuretics , clonidine , or angiotensin-converting-enzyme inhibitors ; evidence of cancer within the past year ; evidence of any uncontrolled cardiovascular , pulmonary , renal , hepatic , endocrine , neurologic , or gastrointestinal disease ; smoking within the preceding 4 weeks ; history of substance abuse ( drug or alcohol ) ; or participation in an investigational drug study within 4 weeks before pretreatment . The patients were required to discontinue certain medications at least 14 days before the first day of the study . Among the disallowed medications were aspirin , dipyridamole , calcium channel blockers , and other vasodilators . Treatment Regimen Iloprost was supplied in ampules containing 0.1 mg of the active drug in 1 mL of a sterile pyrogen-free solution . Placebo ampules contained the same solution without iloprost . Infusion rates of 0.5 to 2.0 ng/kg per minute were used , based on studies showing that 0.5 ng/kg per minute was the usual threshold for the inhibition of platelet aggregation and that infusion rates greater than 2 ng/kg per minute frequently produced side effects . Patients were assigned r and omly to one of two treatment groups , either a  
    Output:
    
We concluded iloprost may lead to little or no difference in the frequency or severity of secondary Raynaud  , and it is associated to adverse effects and important costs