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

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

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

Study Overview

• Status: Recruiting
• Conditions: Infection, Bacterial; Short Bowel Syndrome
• Intervention / Treatment: Drug: Amoxicillin; Drug: Ofloxacin; Drug: Levofloxacin; Drug: Sulfamethoxazole trimethoprim

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 Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lorraine
    • Vandœuvre-lès-Nancy, Lorraine, France, 54500
      • Recruiting
      • CHRU Nancy
      • Contact: Julie LECOMTE; Phone Number: +33383155278; Email: ju.lecomte@chru-nancy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Amoxicillin; 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; Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally
EXPERIMENTAL: Ofloxacin; 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: Ofloxacin; Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally
EXPERIMENTAL: Levofloxacin; 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: Levofloxacin; Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally
EXPERIMENTAL: Sulfamethoxazole trimethoprim; 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: Sulfamethoxazole trimethoprim; Each patient will receive the proper antibiotic to treat the infection, first intravenously, then orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Assess link between length of remaining bowel and antibiotic absorption	Length of remaining bowel (cm)	At inclusion

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Collaborators: Fresenius Kabi; Société Francophone Nutrition Clinique et Métabolisme; FIlière des Maladies rares Abdomino-THOraciques
• Investigators: Principal Investigator: Niasha MICHOT, MD, CHRU Nancy

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Lamp KC, Bailey EM, Rybak MJ. Ofloxacin clinical pharmacokinetics. Clin Pharmacokinet. 1992 Jan;22(1):32-46. doi: 10.2165/00003088-199222010-00004.
• 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.
• 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.
• 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 Res. 2017 Dec;160:76-82. doi: 10.1016/j.thromres.2017.10.025. Epub 2017 Nov 4.
• 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: 10.1177/1060028014526700. Epub 2014 Mar 25.
• 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.
• 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.x.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 9, 2022
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): February 1, 2025

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (ACTUAL): March 31, 2022

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 10, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Postoperative Complications; Disease; Gastrointestinal Diseases; Intestinal Diseases; Bacterial Infections and Mycoses; Malabsorption Syndromes; Syndrome; Bacterial Infections; Short Bowel Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Amoxicillin; Levofloxacin; Ofloxacin; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: 2021-001468-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Depending on first results, this pilot study might be extended in a new multicenter study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No