GRAAL: Absorption of Antibiotics With High Oral Bioavailability in Short-bowel Syndrome
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the drug absorption of oral antibiotics in patients with short bowel syndrome.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
When required, due to an infection, patients with short bowel syndrome will be treated with an intravenous antibiotic. The pharmacokinetic profile of that intravenous antibiotic will be determined. Once the full treatment with the intravenous antibiotic is over, the patient will be orally administered the same antibiotic, with determination of the oral pharmacokinetic profile, and both profiles will be compared, assessing the bioavailability of the oral antibiotic.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Antibiotic arm Each patient will receive the IV antibiotic required to treat the infection, and after the proper duration of the IV antibiotic is over, the patient will receive a few days of the oral version of the same antibiotic. |
Drug: amoxicillin, levofloxacin, ofloxacin, sulfamethoxazole/trimethoprim
Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally
|
Outcome Measures
Primary Outcome Measures
- Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome [Time -0.5 hours]
F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)
- Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome [Time +0.5 hours]
F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)
- Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome [Time +1 hour]
F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)
- Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome [Time +1.5 hour]
F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)
- Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome [Time +2 hours]
F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)
- Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome [Time +4 hours]
F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)
- Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome [Time +6 hours]
F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)
- Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome [Time +8 hours]
F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)
Secondary Outcome Measures
- Describe antibiotic absorption after oral administration in these patients [Time -0.5hour ; Time +0.5hour ; Time +1 hour ; Time+1.5 hour ; Time +2 hours ; Time+4 hours ; Time +6 hours ; Time + 8 hours]
Peak plasma concentration (Cmax) after oral intake
- Describe antibiotic absorption after oral administration in these patients [Time -0.5hour ; Time +0.5hour ; Time +1 hour ; Time+1.5 hour ; Time +2 hours ; Time+4 hours ; Time +6 hours ; Time + 8 hours]
Peak plasma concentration time after oral intake (Tmax)
- Describe antibiotic absorption after oral administration in these patients [Time -0.5hour ; Time +0.5hour ; Time +1 hour ; Time+1.5 hour ; Time +2 hours ; Time+4 hours ; Time +6 hours ; Time + 8 hours]
Area under the plasma concentration versus time curve (AUC)
- Assess link between length of remaining bowel and antibiotic absorption [At inclusion]
Length of remaining bowel (cm)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Short bowel syndrome
-
Treated for a documented infection with antibiogram by amoxicillin (+/- clavulanic acid)or ofloxacin or levofloxacin or sulfamethoxazole/trimethoprim
-
Hospitalized in the Nutritional Assistant Unit or the Infectiology Unit of the Regional University Hospital of Nancy
-
Affiliated to a social security system
-
Having received an physical examination before entering study
-
Having received full information regarding the study organization and having signed the informed consent
Exclusion Criteria:
-
Patient at risk of worsening their oral absorption abilities during study
-
Patient requiring dialysis
-
Women of childbearing age without efficient birth control
-
Allergy to any of the drugs tested
-
Person concerned by Articles L. 1121-5, L. 1121-7 et L1121-8 of the Code of public health
-
Person deprived of liberty or person undergoing psychiatric care pursuant to articles
- 3212-1 et L. 3213-1
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Central Hospital, Nancy, France
- Société Francophone Nutrition Clinique et Métabolisme
- FIlière des Maladies rares Abdomino-THOraciques
- Fresenius Kabi
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- American Gastroenterological Association. American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation. Gastroenterology. 2003 Apr;124(4):1105-10.
- Gupta A, Mehta Y, Juneja R, Trehan N. The effect of cannula material on the incidence of peripheral venous thrombophlebitis. Anaesthesia. 2007 Nov;62(11):1139-42.
- Maki DG, Kluger DM, Crnich CJ. The risk of bloodstream infection in adults with different intravascular devices: a systematic review of 200 published prospective studies. Mayo Clin Proc. 2006 Sep;81(9):1159-71. Review.
- Pironi L, Arends J, Bozzetti F, Cuerda C, Gillanders L, Jeppesen PB, Joly F, Kelly D, Lal S, Staun M, Szczepanek K, Van Gossum A, Wanten G, Schneider SM; Home Artificial Nutrition & Chronic Intestinal Failure Special Interest Group of ESPEN. ESPEN guidelines on chronic intestinal failure in adults. Clin Nutr. 2016 Apr;35(2):247-307. doi: 10.1016/j.clnu.2016.01.020. Epub 2016 Feb 8. Erratum in: Clin Nutr. 2017 Apr;36(2):619.
- Scala-Bertola J, Rabiskova M, Lecompte T, Bonneaux F, Maincent P. Granules in the improvement of oral heparin bioavailability. Int J Pharm. 2009 Jun 5;374(1-2):12-6. doi: 10.1016/j.ijpharm.2009.02.020. Epub 2009 Mar 9.
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