Impact of SPN on Infection Rate, Duration of Mechanical Ventilation & Rehabilitation in ICU Patients

• Sponsor: University Hospital, Geneva (Other)
• Overall Status: Completed
• CT.gov ID: NCT00802503
• Collaborator: University of Lausanne Hospitals (Other)
• Enrollment: 305
• Locations: 2
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 152.5
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

Rationale: Enteral nutrition (EN) in the intensive care (ICU) patients is recommended as a standard of care. However, EN alone is often associated with insufficient energy intakes and increased complication rates. Recently the investigators proposed to decrease this deficit by combining EN and supplemental parenteral nutrition (SPN) whenever EN is insufficient (< 60% of their predicted energy needs) at day 3 after admission in the ICU.

Objective: This study aims at: a/ investigating if the delivery of optimal nutrition support (100 % of predicted energy targets) in ICU patients by the combined administration of SPN and EN optimizes their clinical outcome; b/ implementing the new ICU nutrition guidelines.

Study design: Prospective, controlled, randomized clinical study.

Study site: Service of Intensive Care, Geneva University Hospital.

Patient population: 220 ICU patients to be included: expected length of stay > 5 days, expected survival > 7 days, no contraindication to EN, obtained informed consent from themselves or their next of keen.

Exclusion criteria: refusal of consent, age < 18 years, short bowel syndrome, significant persistent gastrointestinal dysfunction with ileus, high output proximal fistula (> 1,5 liter/d), patients receiving PN.

Nutrition: At day 3 after admission, if energy input is < 60%; patients are randomized into either the "Control group" (EN alone) or the "SPN group" (EN + PN) to reach 100% of their predicted energy needs. Tight glycaemic control (target 6.0 to 8.3 mmol/l) to be achieved according to our local practice by insulin administration.

Study endpoints:

• Primary: nosocomial infections (CDC criteria)

• Secondary: Mechanical ventilation duration, ICU and hospital length of stay, antibiotic free days, ICU complications (extra-renal epuration, neurological, cardiac and respiratory complications), energy and protein balance, 28 days clinical outcome.

Condition or Disease	Intervention/Treatment	Phase
Critically Ill	Dietary Supplement: SPN	Phase 3

Detailed Description

Introduction:

Nutritional support of the intensive care (ICU) patients is recommended as a standard of care. It is also strongly recommended to start enteral feeding as soon as possible whenever the gastrointestinal tract is functioning (1). However, studies have repeatedly shown that with enteral support alone, insufficient energy and protein intakes often occur (2). The resulting energy and protein deficit is associated with an increased complication rate in ICU patients (3-5). Recently we proposed to decrease this deficit by promoting a combined nutrition support by enteral nutrition (EN) and supplemental parenteral nutrition (SPN) whenever EN is insufficient (6).

Contrary to former beliefs, recent meta-analyses show that parenteral nutrition (PN) does not carry excess mortality (7, 8). These reports convey a concept that is a major break-through in current routine of nutritional support in ICU patients by promoting a much wider use of PN. SPN could be the optimal modality to provide the calculated energy targets if this cannot be reached by EN alone. To improve ICU patient's outcome and minimise complications, we propose to implement feeding protocols which combine both EN and PN, when EN is insufficient to cover more than 60% of caloric needs at day 4 to reach 100% of the energy targets by adding PN from day 4 (6).

Hypothesis:

The administration of SPN, in ICU patients receiving < 60% of targeted energy needs by EN alone, has a positive impact on their clinical outcome by optimising their nutritional support (reduced infectious complications rate, mechanical ventilation days, duration of ICU and hospital length of stay and rehabilitation).

Objective:

The aim of the present study is to investigate if the delivery of optimal nutrition support (100 % of predicted energy targets) in ICU patients achieved with the combined administration of SPN and EN optimizes their clinical outcome.

Study Design

• Study Type: Interventional
• Actual Enrollment: 305 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Impact of Supplemental Parenteral Nutrition (SPN) on Infection Rate, Duration of Mechanical Ventilation and Rehabilitation in Intensive Care Unit Patients: A Quality Control Program for the Implementing of New Nutrition Guidelines
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SPN group experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution.	Dietary Supplement: SPN; SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
No Intervention: Control gr EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day1: 500 ml, day2: 1000 ml, day3: 1500 ml of EN dependant on gastrointestinal tolerance (gastric residue volume more than 500ml). Nutritional products as currently used in our institution.

Outcome Measures

Primary Outcome Measures

1. Documented Infection Rate [20 days]

   Infection, defined according to CDC criteria during the ICU and hospital stay, occurrence between day 9 and day 28

Secondary Outcome Measures

1. Hours on Mechanical Ventilation in All Patients [28 days]

   Mechanical ventilation hours during study duration (days 1-28)

2. Antibiotic Free Days [20 days]

   Number of days between day 9 to day 28 (follow-up period) free of antibiotics

3. Total Energy Intake During the Intervention Period , Between Day 4 and Day 8. [5 days]

   Percentage of energy target; in the SPN group the goal was to achieve 100% of the energy target during intervention (day 4 to day 8.The energy target was measured by indirect calorimetry in 198 patients of 305(65%),otherwise energy target was calculated by 25 kcal per kg of ideal body weight for women and 30 kcal per kg of ideal body weight for men and anamnestic body weight was used for patients with a body mass index of 20 kg/m2 or lower.

4. General Mortality [28 days]

5. Days in ICU [28 days]

   Days in ICU

6. ICU Mortality [28 days]

7. Protein Delivery During the Intervention Period From Day 4 to Day 8 [5 days]

   Percentage of protein target between day 4 to 8. Protein target was set to 1.2 g per kg of ideal body weight a day.

8. Days in Hospital [28 days]

   hospital length of stay

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Expected ICU stay > 5 days

• Expected survival > 7 days

• No contraindication to EN

• Obtained informed consent

Exclusion Criteria:

• Refusal of consent

• Age < 18 years

• Short bowel syndrome

• Significant persistent gastrointestinal dysfunction with ileus

• High output proximal fistula (> 1.5 liter/d)

• Patients receiving PN

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Service of Intensive Care, Geneva University Hospital,	Geneva		Switzerland	1211
2	Service de Médecine Intensive Adulte et Centre des Brûlés	Lausanne		Switzerland	1011

Sponsors and Collaborators

• University Hospital, Geneva
• University of Lausanne Hospitals

Investigators

• Principal Investigator: Claudia P HEIDEGGER, MD, Division of Intensive Care, 1211 Geneva 14, Switzerland

Study Documents (Full-Text)

None provided.

More Information

Publications

• Heidegger CP, Romand JA, Treggiari MM, Pichard C. Is it now time to promote mixed enteral and parenteral nutrition for the critically ill patient? Intensive Care Med. 2007 Jun;33(6):963-9. Epub 2007 Apr 28.

• Responsible Party: HEIDEGGER CP, Deputy head physician, University Hospital, Geneva
• ClinicalTrials.gov Identifier: NCT00802503
• Other Study ID Numbers: Protocole 07-098
• First Posted: Dec 5, 2008
• Last Update Posted: Apr 19, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by HEIDEGGER CP, Deputy head physician, University Hospital, Geneva: Critically ill; nutrition; randomised controlled clinical trial; human; adult; Supplemental parenteral nutrition
• Additional relevant MeSH terms: Critical Illness

Study Results

Participant Flow

Arm/Group Title	Control Group	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day1: 500 ml, day2: 1000 ml, day3: 1500 ml of EN dependant on gastrointestinal tolerance (gastric residue volume more than 500ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Period Title: Overall Study
STARTED	152	153
COMPLETED	142	133
NOT COMPLETED	10	20

Baseline Characteristics

Arm/Group Title	Control gr	SPN Group	Total
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day1: 500 ml, day2: 1000 ml, day3: 1500 ml of EN dependant on gastrointestinal tolerance (gastric residue volume more than 500ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.	Total of all reporting groups
Overall Participants	152	153	305
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	91 59.9%	83 54.2%	174 57%
>=65 years	61 40.1%	70 45.8%	131 43%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (16)	61 (16)	60 (17)
Sex: Female, Male (Count of Participants)
Female	47 30.9%	43 28.1%	90 29.5%
Male	105 69.1%	110 71.9%	215 70.5%
Region of Enrollment (participants) [Number]
Switzerland	152 100%	153 100%	305 100%

Outcome Measures

1. Primary Outcome

Title	Documented Infection Rate
Description	Infection, defined according to CDC criteria during the ICU and hospital stay, occurrence between day 9 and day 28
Time Frame	20 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control gr	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day 1: 500 ml, day 2: 1000 ml, day 3: 1500 ml of EN dependent on gastrointestinal tolerance (gastric residue volume more than 500 ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Number [Infections]	58	41

2. Secondary Outcome

Title	Hours on Mechanical Ventilation in All Patients
Description	Mechanical ventilation hours during study duration (days 1-28)
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The intention to treat analysis included all patients randomly assigned to the intervention SPN group (153) or control group EN (152). The per protocol analysis included only patients who fully completed the 5-day intervention in the ICU (SPN group(133); EN group (142).

Arm/Group Title	Control gr	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day 1: 500 ml, day 2: 1000 ml, day 3: 1500 ml of EN dependent on gastrointestinal tolerance (gastric residue volume more than 500 ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Mean (95% Confidence Interval) [hours of mechanical ventilation]	166	153

3. Secondary Outcome

Title	Antibiotic Free Days
Description	Number of days between day 9 to day 28 (follow-up period) free of antibiotics
Time Frame	20 days

Outcome Measure Data

Analysis Population Description

The intention to treat analysis included all patients randomly assigned to the intervention SPN group (153) or control group EN (152). The per protocol analysis included only patients who fully completed the 5-day intervention in the ICU (SPN group(133); EN group (142).

Arm/Group Title	Control gr	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day 1: 500 ml, day 2: 1000 ml, day 3: 1500 ml of EN dependent on gastrointestinal tolerance (gastric residue volume more than 500 ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Mean (95% Confidence Interval) [number of days]	12	14

4. Secondary Outcome

Title	Total Energy Intake During the Intervention Period , Between Day 4 and Day 8.
Description	Percentage of energy target; in the SPN group the goal was to achieve 100% of the energy target during intervention (day 4 to day 8.The energy target was measured by indirect calorimetry in 198 patients of 305(65%),otherwise energy target was calculated by 25 kcal per kg of ideal body weight for women and 30 kcal per kg of ideal body weight for men and anamnestic body weight was used for patients with a body mass index of 20 kg/m2 or lower.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

The intention to treat analysis included all patients randomly assigned to the intervention SPN group (153) or control group EN (152). The per protocol analysis included only patients who fully completed the 5-day intervention in the ICU (SPN group(133); EN group (142).

Arm/Group Title	Control gr	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day 1: 500 ml, day 2: 1000 ml, day 3: 1500 ml of EN dependent on gastrointestinal tolerance (gastric residue volume more than 500 ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Mean (Standard Deviation) [% of energy target]	77 (27)	103 (18)

5. Secondary Outcome

Title	General Mortality
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The intention to treat analysis included all patients randomly assigned to the intervention SPN group (153) or control group EN (152). The per protocol analysis included only patients who fully completed the 5-day intervention in the ICU (SPN group(133); EN group (142).

Arm/Group Title	Control Group	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day 1: 500 ml, day 2: 1000 ml, day 3: 1500 ml of EN dependent on gastrointestinal tolerance (gastric residue volume more than 500 ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Number [participants]	28 (18) 18.4%	20 (13) 13.1%

6. Secondary Outcome

Title	Days in ICU
Description	Days in ICU
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The intention to treat analysis included all patients randomly assigned to the intervention SPN group (153) or control group EN (152). The per protocol analysis included only patients who fully completed the 5-day intervention in the ICU (SPN group(133); EN group (142).

Arm/Group Title	Control gr	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day 1: 500 ml, day 2: 1000 ml, day 3: 1500 ml of EN dependent on gastrointestinal tolerance (gastric residue volume more than 500 ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Mean (95% Confidence Interval) [days in ICU]	13	13

7. Secondary Outcome

Title	ICU Mortality
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The intention to treat analysis included all patients randomly assigned to the intervention SPN group (153) or control group EN (152). The per protocol analysis included only patients who fully completed the 5-day intervention in the ICU (SPN group(133); EN group (142).

Arm/Group Title	Control gr	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day 1: 500 ml, day 2: 1000 ml, day 3: 1500 ml of EN dependent on gastrointestinal tolerance (gastric residue volume more than 500 ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Number [participants]	12 7.9%	8 5.2%

8. Secondary Outcome

Title	Protein Delivery During the Intervention Period From Day 4 to Day 8
Description	Percentage of protein target between day 4 to 8. Protein target was set to 1.2 g per kg of ideal body weight a day.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

The intention to treat analysis included all patients randomly assigned to the intervention SPN group (153) or control group EN (152). The per protocol analysis included only patients who fully completed the 5-day intervention in the ICU (SPN group(133); EN group (142).

Arm/Group Title	Controle gr	SPN gr
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day 1: 500 ml, day 2: 1000 ml, day 3: 1500 ml of EN dependent on gastrointestinal tolerance (gastric residue volume more than 500 ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Mean (Standard Deviation) [percentage of protein target]	71 (27)	100 (16)

9. Secondary Outcome

Title	Days in Hospital
Description	hospital length of stay
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

The intention to treat analysis included all patients randomly assigned to the intervention SPN group (153) or control group EN (152). The per protocol analysis included only patients who fully completed the 5-day intervention in the ICU (SPN group(133); EN group (142).

Arm/Group Title	Control gr	SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day1: 500 ml, day2: 1000 ml, day3: 1500 ml of EN dependant on gastrointestinal tolerance (gastric residue volume more than 500ml). Nutritional products as currently used in our institution.	experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
Measure Participants	152	153
Mean (95% Confidence Interval) [days in hospital]	32	31

Adverse Events

Time Frame	The follow up period was until day 28.
Adverse Event Reporting Description	No adverse events were observed during the intervention period from day 4 to day 8.
Arm/Group Title	Control gr		SPN Group
Arm/Group Description	EN : start EN at 20-30 ml/h per day up to maximal 150 ml/h per day; or day1: 500 ml, day2: 1000 ml, day3: 1500 ml of EN dependant on gastrointestinal tolerance (gastric residue volume more than 500ml). Nutritional products as currently used in our institution.		experimental arm: Supplemental Parenteral Nutrition (SPN) is added to enteral nutrition (EN) to reach 100% of their predicted energy needs from ICU day 4. In the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line. Nutritional products as currently used in our institution. SPN is composed of EN and PN, both techniques being currently used in our institution. SPN : SPN : in the treated group, SPN is started if at day 4 energy input by EN is < 60% of energy target in order to reach 100% of energy target by peripheral or central line.
All Cause Mortality
	Control gr		SPN Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Control gr		SPN Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/152 (0%)		0/153 (0%)
Other (Not Including Serious) Adverse Events
	Control gr		SPN Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/152 (0%)		0/153 (0%)

Limitations/Caveats

The trial was limited by the fact that it was not double blinded by design. However, the risk of bias was reduced because the investigators worked independently from the physicians in charge of the patients.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.