Bovine Lactoferrin as a Natural Regimen of Selective Decontamination of the Digestive Tract in Patients With Prolonged Mechanical Ventilation

NCT01535170 | Unknown DMC

• 1 other identifier: DMR99-IRB-076
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

Nosocomial infection with antibiotic-resistant strains is a major threat to critical care medicine. Selective decontamination of the digestive tract (SDD) is one of the strategies to reduce ventilator associated pneumonia and sepsis in critically ill patients. Lactoferrin (LF) is a natural multifunctional protein with antimicrobial, anti-tumor, antioxidant, and immunomodulatory effects. It has been shown to inhibit the growth of a number of pathogenic bacteria including antibiotic-resistant strains, fungi and even viruses in both in vitro and in vivo studies. In a recent study, the investigators performed pathogen challenges of the digestive tract of a transgenic milk-fed animal model. The results showed that recombinant LF has broad spectrum antimicrobial activity in the digestive tract and protects the mucosa of the small intestine from injury, implying that LF can be used as an effective selective decontaminant of the digestive tract. This study is a prospective, randomized, double-blind, placebo- controlled clinical trial examining whether oral supplementation with bLF can reduce nosocomial infection, sepsis and even mortality in patients with prolonged mechanical ventilation (MV). Patients with MV for more than 21 days and no signs of infection on admission to our Respiratory Care Center (RCC) will be enrolled. They will be randomized to receive either bovine LF (bLF, 10 mg/kg/day) or placebo for 6 weeks by center. The primary objective is to evaluate the effectiveness of bLF in the prevention of nosocomial infection. Secondary objectives are assessment of incidence of nosocomial infection, mortality, weaning rate from MV and change of the immune system. The investigators hypothesize that bLF may 1) prevent nosocomial infection; 2) reduce mortality; 3)increase weaning rate from MV; 4)increase immunity in patients with prolonged MV.

Conditions

Nosocomial Infections

Keywords

lactoferrin; selective decontamination of digestive tract; antimicrobial activity; prolonged mechanical ventilation; respiratory care center

Outcome Measures

Primary Outcomes (1)

• Prevention of infection

  To evaluate the effectiveness of bLF in the prevention of the first episode of nosocomial infection and sepsis

  30 days

Secondary Outcomes (2)

• Effects on infection

  30 days

• Effects on immunity

  30 days

Study Arms (2)

bovine Lactoferrin

EXPERIMENTAL

Lactoferrin and placebo will be masked as drug A and B in the factory. Randomization will be stratified by center and patients will be randomized into A or B groups by a random-number table sequence after informed consents are obtained. No patients, research nurses, investigators, or other medical staffs in RCC will be aware of the assignment during the study period. Patients will receive either bLF (10 mg/Kg/day) (Westland Co-operative Dairy Company, New Zealand) or placebo (starch) as control. The dosage of bLF is based on the mean hLF intake that very low body weight neonates ingest with mother's fresh milk in the first 2 weeks of life (30-150 mg/d) \[16\] and bLF 200 mg bid is found to be effective to suppress Helicobacter pylori \[17\]. Drug administration will begin within 24 hours after RCC admission and will last for 6 weeks or until discharge. Medication and nutritional support will be prescribed as the medical routine.

Dietary Supplement: bovine Lactoferrin

Placebo

PLACEBO COMPARATOR

Patients will receive either bLF (10 mg/Kg/day) (Westland Co-operative Dairy Company, New Zealand) or placebo (starch) as control.

Dietary Supplement: bovine Lactoferrin

Interventions

bovine Lactoferrin DIETARY_SUPPLEMENT

Patients will receive either bLF (10 mg/Kg/day) (Westland Co-operative Dairy Company, New Zealand) or placebo (starch) as control. The dosage of bLF is based on the mean hLF intake that very low body weight neonates ingest with mother's fresh milk in the first 2 weeks of life (30-150 mg/d) \[16\] and bLF 200 mg bid is found to be effective to suppress Helicobacter pylori \[17\].

Placebo; bovine Lactoferrin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with mechanical ventilation for more than 21 days and no evident signs of infection in our Respiratory Care Center (RCC).

You may not qualify if:

• Informed consent lacking/refused
• Ongoing antibiotics treatment for infection
• Predicted mortality in 7 days.

Sponsors & Collaborators

• China Medical University Hospital: lead

Study Sites (1)

Department of Internal Medicine, China Medical Univdersity Hospital

Taichung, Taiwan, Taiwan

RECRUITING

Related Publications (17)

• Yen CC, Lin CY, Chong KY, Tsai TC, Shen CJ, Lin MF, Su CY, Chen HL, Chen CM. Lactoferrin as a natural regimen for selective decontamination of the digestive tract: recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonates from pathogenic challenge in the gastrointestinal tract. J Infect Dis. 2009 Feb 15;199(4):590-8. doi: 10.1086/596212.

  PMID: 19125673 BACKGROUND

• Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005 Oct;33(10):2184-93. doi: 10.1097/01.ccm.0000181731.53912.d9.

  PMID: 16215368 BACKGROUND

• Jones RN. Resistance patterns among nosocomial pathogens: trends over the past few years. Chest. 2001 Feb;119(2 Suppl):397S-404S. doi: 10.1378/chest.119.2_suppl.397s.

  PMID: 11171776 BACKGROUND

• de Jonge E, Schultz MJ, Spanjaard L, Bossuyt PM, Vroom MB, Dankert J, Kesecioglu J. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet. 2003 Sep 27;362(9389):1011-6. doi: 10.1016/S0140-6736(03)14409-1.

  PMID: 14522530 BACKGROUND

• Bonten MJ, Grundmann H. Selective digestive decontamination and antibiotic resistance: a balancing act. Crit Care Med. 2003 Aug;31(8):2239-40. doi: 10.1097/01.CCM.0000080491.46005.3F. No abstract available.

  PMID: 12973186 BACKGROUND

• Pittet D, Eggimann P, Rubinovitch B. Prevention of ventilator-associated pneumonia by oral decontamination: just another SDD study? Am J Respir Crit Care Med. 2001 Aug 1;164(3):338-9. doi: 10.1164/ajrccm.164.3.2105072b. No abstract available.

  PMID: 11500329 BACKGROUND

• Camus C, Bellissant E, Sebille V, Perrotin D, Garo B, Legras A, Renault A, Le Corre P, Donnio PY, Gacouin A, Le Tulzo Y, Thomas R. Prevention of acquired infections in intubated patients with the combination of two decontamination regimens. Crit Care Med. 2005 Feb;33(2):307-14. doi: 10.1097/01.ccm.0000152224.01949.01.

  PMID: 15699832 BACKGROUND

• Vincent JL. Selective digestive decontamination: for everyone, everywhere? Lancet. 2003 Sep 27;362(9389):1006-7. doi: 10.1016/S0140-6736(03)14445-5. No abstract available.

  PMID: 14522525 BACKGROUND

• Valenti P, Antonini G. Lactoferrin: an important host defence against microbial and viral attack. Cell Mol Life Sci. 2005 Nov;62(22):2576-87. doi: 10.1007/s00018-005-5372-0.

  PMID: 16261253 BACKGROUND

• Tomita M, Wakabayashi H, Yamauchi K, Teraguchi S, Hayasawa H. Bovine lactoferrin and lactoferricin derived from milk: production and applications. Biochem Cell Biol. 2002;80(1):109-12. doi: 10.1139/o01-230.

  PMID: 11908633 BACKGROUND

• Kim WS, Ohashi M, Tanaka T, Kumura H, Kim GY, Kwon IK, Goh JS, Shimazaki K. Growth-promoting effects of lactoferrin on L. acidophilus and Bifidobacterium spp. Biometals. 2004 Jun;17(3):279-83. doi: 10.1023/b:biom.0000027705.57430.f1.

  PMID: 15222478 BACKGROUND

• Chen HL, Lai YW, Yen CC, Lin YY, Lu CY, Yang SH, Tsai TC, Lin YJ, Lin CW, Chen CM. Production of recombinant porcine lactoferrin exhibiting antibacterial activity in methylotrophic yeast, Pichia pastoris. J Mol Microbiol Biotechnol. 2004;8(3):141-9. doi: 10.1159/000085787.

  PMID: 16088216 BACKGROUND

• Chen HL, Yen CC, Lu CY, Yu CH, Chen CM. Synthetic porcine lactoferricin with a 20-residue peptide exhibits antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans. J Agric Food Chem. 2006 May 3;54(9):3277-82. doi: 10.1021/jf053031s.

  PMID: 16637685 BACKGROUND

• Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, Stolfi I, Decembrino L, Laforgia N, Vagnarelli F, Memo L, Bordignon L, Saia OS, Maule M, Gallo E, Mostert M, Magnani C, Quercia M, Bollani L, Pedicino R, Renzullo L, Betta P, Mosca F, Ferrari F, Magaldi R, Stronati M, Farina D; Italian Task Force for the Study and Prevention of Neonatal Fungal Infections, Italian Society of Neonatology. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA. 2009 Oct 7;302(13):1421-8. doi: 10.1001/jama.2009.1403.

  PMID: 19809023 BACKGROUND

• Okuda M, Nakazawa T, Yamauchi K, Miyashiro E, Koizumi R, Booka M, Teraguchi S, Tamura Y, Yoshikawa N, Adachi Y, Imoto I. Bovine lactoferrin is effective to suppress Helicobacter pylori colonization in the human stomach: a randomized, double-blind, placebo-controlled study. J Infect Chemother. 2005 Dec;11(6):265-9. doi: 10.1007/s10156-005-0407-x.

  PMID: 16369731 BACKGROUND

• Mulder AM, Connellan PA, Oliver CJ, Morris CA, Stevenson LM. Bovine lactoferrin supplementation supports immune and antioxidant status in healthy human males. Nutr Res. 2008 Sep;28(9):583-9. doi: 10.1016/j.nutres.2008.05.007.

  PMID: 19083463 BACKGROUND

• Teraguchi S, Wakabayashi H, Kuwata H, Yamauchi K, Tamura Y. Protection against infections by oral lactoferrin: evaluation in animal models. Biometals. 2004 Jun;17(3):231-4. doi: 10.1023/b:biom.0000027697.83706.32.

  PMID: 15222470 BACKGROUND

MeSH Terms

Conditions

Cross Infection

Condition Hierarchy (Ancestors)

Infections; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Chih-Ching Yen, MD, PhD

CONTACT

886-4-22-52121; D5210@mail.cmuh.org.tw

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 15, 2011
• First Posted: February 17, 2012
• Study Start: September 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: July 1, 2012
• Last Updated: February 17, 2012

Record last verified: 2012-02

Locations

TW (1)