C-C: Effect of Goal-directed Crystalloid Versus Colloid Administration on Major Postoperative Morbidity

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01195883
• Collaborator: (none)
• Enrollment: 1,102
• Locations: 3
• Arms: 2
• Duration (Months): 83.6
• Patients Per Site: 367.3
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

A trial in which patients having open abdominal surgery are randomized to receive either crystalloids or colloids intraoperatively, guided by esophageal Doppler. The investigators test the primary hypothesis that goal-directed colloid administration during elective abdominal surgery decreases a composite of postoperative complications within 30 days of surgery.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Complications	Drug: Crystalloid; Drug: Colloid	N/A

Detailed Description

Patients will be given 5-7 ml/kg of crystalloid (lactated Ringer's) in the immediate preoperative period, which will be followed by 4 ml/kg/h crystalloid for maintenance normalized to ideal body weight [Men: Ideal Body Weight (in kilograms) = 52 kg + 1.9 kg for every 2.5 cm over 150 cm; Women: Ideal Body Weight (in kilograms) = 49 kg + 1.7 kg for every 2.5 cm over 150 cm].

They will then be randomly assigned to additional volume replacement, guided by esophageal Doppler, to either lactated Ringer's solution of Voluven starch.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Goal-directed Crystalloid Versus Colloid Administration on Major Postoperative Morbidity
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Oct 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Crystalloid Lactated Ringers solution will be used for fluid replacement.	Drug: Crystalloid; For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.; Other Names: Ringer's lactate Lactated Ringer's solution
Active Comparator: Colloid Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement	Drug: Colloid; For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.; Other Names: Voluven

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Postoperative Morbidity (Major Complications) [Postoperative 30-days]

   Any of the following major complications: (1) Cardiac (Acute heart failure/Myocardial infarction/Ventricular arrhythmia); (2) pulmonary (embolism/edema/respiratory failure/pneumonia/pleural effusion); (3) gastrointestinal (bowel and surgical anastomosis stricture or anastomotic leak/internal or external fistulas/peritoneal effusions); (4) Renal (requiring dialysis); (5) Infectious (deep or organ space surgical site infection / sepsis); and (6) Coagulation (bleeding).

Secondary Outcome Measures

1. Number of Participants With Postoperative Morbidity (Minor Complications) [Postoperative 30-days]

   Any of the following minor complications: (1) unplanned ICU admission; (2) unplanned operation; (3) cardiac (ischemia/non-ventricular arrhythmia/hemodynamic disturbances); (4) pulmonary effusion; (5) deep venous thrombosis; (6) gastrointestinal (effusion/gut paralysis); (7) progressive renal insufficiency; (8) infection (superficial/fever/cystitis or urinary tract infection); and (9) transient neurological injury.

2. Number of Participants With Postoperative Complications, 30-day Readmission, and 30-day Death [Postoperative 30 days]

   A composite of the primary outcome, and readmission and death.

3. Number of Participants With Postoperative Acute Kidney Injury [Hospitalization]

   Preoperative-to-postoperative change in AKIN stage

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ASA Physical Status 1-3

• Body Mass Index < 35

• Moderate risk elective abdominal surgical procedures scheduled to take ≥ two hours done under general anesthesia.

Exclusion Criteria:

• cardiac insufficiency (EF<35%)

• coronary disease with angina (NYHA IV)

• severe chronic obstructive pulmonary disease

• coagulopathies

• symptoms of infection or sepsis

• renal insufficiency (creatinine clearance <30ml/min or renal replacement therapy)

• ASA Physical Status > 3.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
2	Cleveland Clinic Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
3	Medical University of Vienna	Vienna		Austria	1090

Sponsors and Collaborators

• The Cleveland Clinic

Investigators

• Principal Investigator: Andrea Kurz, MD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT01195883
• Other Study ID Numbers: 09-1051
• First Posted: Sep 6, 2010
• Last Update Posted: Oct 30, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by The Cleveland Clinic: IV fluid; recovery; goal directed fluid replacement; improved patient recovery
• Additional relevant MeSH terms: Postoperative Complications

Study Results

Participant Flow

Arm/Group Title	Crystalloid	Colloid
Arm/Group Description	Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Period Title: Overall Study
STARTED	553	549
COMPLETED	534	523
NOT COMPLETED	19	26

Baseline Characteristics

Arm/Group Title	Crystalloid	Colloid	Total
Arm/Group Description	Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.	Total of all reporting groups
Overall Participants	534	523	1057
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (16)	52 (16)	52 (16)
Sex: Female, Male (Count of Participants)
Female	268 50.2%	242 46.3%	510 48.2%
Male	266 49.8%	281 53.7%	547 51.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Postoperative Morbidity (Major Complications)
Description	Any of the following major complications: (1) Cardiac (Acute heart failure/Myocardial infarction/Ventricular arrhythmia); (2) pulmonary (embolism/edema/respiratory failure/pneumonia/pleural effusion); (3) gastrointestinal (bowel and surgical anastomosis stricture or anastomotic leak/internal or external fistulas/peritoneal effusions); (4) Renal (requiring dialysis); (5) Infectious (deep or organ space surgical site infection / sepsis); and (6) Coagulation (bleeding).
Time Frame	Postoperative 30-days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crystalloid	Colloid
Arm/Group Description	Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Measure Participants	534	523
Count of Participants [Participants]	103 19.3%	91 17.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crystalloid, Colloid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.65 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Postoperative Morbidity (Minor Complications)
Description	Any of the following minor complications: (1) unplanned ICU admission; (2) unplanned operation; (3) cardiac (ischemia/non-ventricular arrhythmia/hemodynamic disturbances); (4) pulmonary effusion; (5) deep venous thrombosis; (6) gastrointestinal (effusion/gut paralysis); (7) progressive renal insufficiency; (8) infection (superficial/fever/cystitis or urinary tract infection); and (9) transient neurological injury.
Time Frame	Postoperative 30-days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crystalloid	Colloid
Arm/Group Description	Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Measure Participants	463	447
Count of Participants [Participants]	234 43.8%	214 40.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crystalloid, Colloid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Postoperative Complications, 30-day Readmission, and 30-day Death
Description	A composite of the primary outcome, and readmission and death.
Time Frame	Postoperative 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crystalloid	Colloid
Arm/Group Description	Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Measure Participants	525	518
Count of Participants [Participants]	143 26.8%	125 23.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crystalloid, Colloid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With Postoperative Acute Kidney Injury
Description	Preoperative-to-postoperative change in AKIN stage
Time Frame	Hospitalization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Crystalloid	Colloid
Arm/Group Description	Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Measure Participants	527	521
Count of Participants [Participants]	21 3.9%	16 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crystalloid, Colloid
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 0.69 to 2.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	30-days postoperative
Adverse Event Reporting Description	Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Arm/Group Title	Crystalloid		Colloid
Arm/Group Description	Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.		Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
All Cause Mortality
	Crystalloid		Colloid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/534 (0.7%)		5/523 (1%)
Serious Adverse Events
	Crystalloid		Colloid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	103/534 (19.3%)		91/523 (17.4%)
Cardiac disorders
Cardiac	8/534 (1.5%)	8	1/523 (0.2%)	1
Gastrointestinal disorders
Gastrointestinal	51/534 (9.6%)	51	41/523 (7.8%)	41
Infections and infestations
infections	58/534 (10.9%)	58	59/523 (11.3%)	59
Renal and urinary disorders
Renal	4/534 (0.7%)	4	2/523 (0.4%)	2
Respiratory, thoracic and mediastinal disorders
Pulmonary	24/534 (4.5%)	24	17/523 (3.3%)	17
Vascular disorders
Coagulation	12/534 (2.2%)	12	16/523 (3.1%)	16
Other (Not Including Serious) Adverse Events
	Crystalloid		Colloid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	234/534 (43.8%)		214/523 (40.9%)
Cardiac disorders
Cardiac	46/534 (8.6%)	46	35/523 (6.7%)	35
Gastrointestinal disorders
Gastrointestinal	103/534 (19.3%)	103	75/523 (14.3%)	75
Infections and infestations
Infection	151/534 (28.3%)	151	139/523 (26.6%)	139
Respiratory, thoracic and mediastinal disorders
Pulmonary effusion	46/534 (8.6%)	46	38/523 (7.3%)	38
Surgical and medical procedures
Minor unplanned operation	23/534 (4.3%)	23	29/523 (5.5%)	29

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.