Absorption of Antibiotics With High Oral Bioavailability in Short-bowel Syndrome

Short Bowel Syndrome Clinical Trial

— GRAAL  

Official title:

Absorption of Antibiotics With High Oral Bioavailability in Short-bowel Syndrome : a Monocentric Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05302531
• Other study ID #: 2021-001468-13
• Status: Recruiting
• Phase: Phase 1
• Start date: December 9, 2022
• Est. completion date: February 2025

Study information

• Verified date: February 2023
• Source: Central Hospital, Nancy, France
• Contact: Niasha MICHOT, MD
• Phone: +33383155108
• Email: n.michot[@]chru-nancy.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the drug absorption of oral antibiotics in patients with short bowel syndrome.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: February 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 L. 3212-1 et L. 3213-1

Related Conditions & MeSH terms

• Bacterial Infections
• Infection, Bacterial
• Short Bowel Syndrome
• Syndrome

Intervention

Drug:
• Amoxicillin
Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally
• Levofloxacin
Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally
• Ofloxacin
Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally
• Sulfamethoxazole trimethoprim
Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally

Locations

Country	Name	City	State
France	CHRU Nancy	Vandœuvre-lès-Nancy	Lorraine

Sponsors (4)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France	FIlière des Maladies rares Abdomino-THOraciques, Fresenius Kabi, Société Francophone Nutrition Clinique et Métabolisme

Country where clinical trial is conducted

France, 

References & Publications (15)

American Gastroenterological Association. American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation. Gastroenterology. 2003 Apr;124(4):1105-10. doi: 10.1053/gast.2003.50139. No abstract available. — View Citation

Barr WH, Zola EM, Candler EL, Hwang SM, Tendolkar AV, Shamburek R, Parker B, Hilty MD. Differential absorption of amoxicillin from the human small and large intestine. Clin Pharmacol Ther. 1994 Sep;56(3):279-85. doi: 10.1038/clpt.1994.138. — View Citation

Cheung YW, Barco S, Mathot RAA, van den Dool EJ, Stroobants AK, Serlie MJ, Middeldorp S, Coppens M. Pharmacokinetics of dabigatran etexilate and rivaroxaban in patients with short bowel syndrome requiring parenteral nutrition: The PDER PAN study. Thromb R — View Citation

Faye E, Drouet L, De Raucourt E, Green A, Bal-Dit-Sollier C, Boudaoud L, Corcos O, Bergmann JF, Joly F, Lloret-Linares C. Absorption and efficacy of acetylsalicylic acid in patients with short bowel syndrome. Ann Pharmacother. 2014 Jun;48(6):705-10. doi: — View Citation

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. doi: 10.1111/j.1365-2044.2007.05180.x. — View Citation

Lamp KC, Bailey EM, Rybak MJ. Ofloxacin clinical pharmacokinetics. Clin Pharmacokinet. 1992 Jan;22(1):32-46. doi: 10.2165/00003088-199222010-00004. — View Citation

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. doi: 10.4065/81.9.1159. — View Citation

Menardi G, Guggenbichler JP. Bioavailability of oral antibiotics in children with short-bowel syndrome. J Pediatr Surg. 1984 Feb;19(1):84-6. doi: 10.1016/s0022-3468(84)80023-8. — View Citation

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. — View Citation

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. — View Citation

Severijnen R, Bayat N, Bakker H, Tolboom J, Bongaerts G. Enteral drug absorption in patients with short small bowel : a review. Clin Pharmacokinet. 2004;43(14):951-62. doi: 10.2165/00003088-200443140-00001. — View Citation

Thielke J, Martin J, Weber FL, Schroeder TJ, Goretsky S, Hanto DW. Pharmacokinetics of tacrolimus and cyclosporine in short-bowel syndrome. Liver Transpl Surg. 1998 Sep;4(5):432-4. doi: 10.1002/lt.500040502. No abstract available. — View Citation

Ueno T, Tanaka A, Hamanaka Y, Suzuki T. Serum drug concentrations after oral administration of paracetamol to patients with surgical resection of the gastrointestinal tract. Br J Clin Pharmacol. 1995 Mar;39(3):330-2. doi: 10.1111/j.1365-2125.1995.tb04457. — View Citation

Vance-Bryan K, Guay DR, Rotschafer JC. Clinical pharmacokinetics of ciprofloxacin. Clin Pharmacokinet. 1990 Dec;19(6):434-61. doi: 10.2165/00003088-199019060-00003. — View Citation

Ward N. The impact of intestinal failure on oral drug absorption: a review. J Gastrointest Surg. 2010 Jun;14(6):1045-51. doi: 10.1007/s11605-009-1151-9. Epub 2010 Jan 22. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome	F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)	Time -0.5 hours
Primary	Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome	F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)	Time +0.5 hours
Primary	Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome	F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)	Time +1 hour
Primary	Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome	F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)	Time +1.5 hour
Primary	Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome	F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)	Time +2 hours
Primary	Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome	F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)	Time +4 hours
Primary	Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome	F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)	Time +6 hours
Primary	Assess the bioavailability of the oral antibiotic in patient with short bowel syndrome	F (%)=(ASC PO)/(ASC IV) x (Dose IV)/(Dose PO)	Time +8 hours
Secondary	Describe antibiotic absorption after oral administration in these patients	Peak plasma concentration (Cmax) after oral intake	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
Secondary	Describe antibiotic absorption after oral administration in these patients	Peak plasma concentration time after oral intake (Tmax)	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
Secondary	Describe antibiotic absorption after oral administration in these patients	Area under the plasma concentration versus time curve (AUC)	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
Secondary	Assess link between length of remaining bowel and antibiotic absorption	Length of remaining bowel (cm)	At inclusion