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

• ClinicalTrials.gov Identifier: NCT01535170
• Recruitment Status: Unknown
• First Posted: February 17, 2012
• Last Update Posted: February 17, 2012
• Sponsor: China Medical University Hospital
• Information provided by: China Medical University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Nosocomial Infections	Dietary Supplement: bovine Lactoferrin	Not Applicable

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Bovine Lactoferrin as a Natural Regimen of Selective Decontamination of the Digestive Tract in Patients With Prolonged Mechanical Ventilation
• Study Start Date: September 2010
• Estimated Primary Completion Date: May 2012
• Estimated Study Completion Date: July 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: bovine Lactoferrin; 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; 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 Comparator: Placebo; 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; 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].

Outcome Measures

Primary Outcome Measures :

1. Prevention of infection [ Time Frame: 30 days ]
   To evaluate the effectiveness of bLF in the prevention of the first episode of nosocomial infection and sepsis

Secondary Outcome Measures :

1. Effects on infection [ Time Frame: 30 days ]
   assessments of the incidence of pneumonia, urinary tract infection.
2. Effects on immunity [ Time Frame: 30 days ]
   alteration of immune system, cytokines

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Contacts

Contact: Chih-Ching Yen, MD, PhD; 886-4-22-52121 ext 3483; D5210@mail.cmuh.org.tw

Locations

Taiwan

Department of Internal Medicine, China Medical Univdersity Hospital; Recruiting

Taichung, Taiwan

Contact: Chih-Chihng Yen, MD, PhD 886-4-22052121 ext 3483 d5210@mail.cmuh.org.tw

Principal Investigator: Chih-Ching Yen, MD, PhD

Sponsors and Collaborators

China Medical University Hospital

More Information

Publications:

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.

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. Review.

Jones RN. Resistance patterns among nosocomial pathogens: trends over the past few years. Chest. 2001 Feb;119(2 Suppl):397S-404S. Review.

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.

Bonten MJ, Grundmann H. Selective digestive decontamination and antibiotic resistance: a balancing act. Crit Care Med. 2003 Aug;31(8):2239-40.

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.

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.

Vincent JL. Selective digestive decontamination: for everyone, everywhere? Lancet. 2003 Sep 27;362(9389):1006-7.

Valenti P, Antonini G. Lactoferrin: an important host defence against microbial and viral attack. Cell Mol Life Sci. 2005 Nov;62(22):2576-87. Review.

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. Review.

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.

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.

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.

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.

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.

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.

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. Review.

• Responsible Party: Deapartment of Medical Research, China Medical University Hospital
• ClinicalTrials.gov Identifier: NCT01535170 History of Changes
• Other Study ID Numbers: DMR99-IRB-076
• First Posted: February 17, 2012
• Last Update Posted: February 17, 2012
• Last Verified: February 2012

Keywords provided by China Medical University Hospital:

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

Additional relevant MeSH terms:

Cross Infection; Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Lactoferrin; Anti-Infective Agents