Blood Management in Orthopedic Surgery (TOMaat)

Optimal Blood Management in Elective Orthopaedic Surgery: The Transfusion "Op Maat" (TOMaat) Study

Aim: to investigate whether the use of several transfusion alternatives (erythropoietin, the cell-saver or postoperative drainage and reinfusion systems) in patients undergoing elective total knee or hip replacement surgery can lead to allogeneic red blood cell (RBC) saving if a restrictive transfusion policy is used.

Study design: a prospective, double randomized, open, multicenter study in which patients are stratified according to their preoperative hemoglobin(Hb) level: stratum I= Hb between 6,1 and 8,2 mmol/l. These patients are first randomized for Erythropoetin (Epo) or no Epo.

Stratum II= Hb of 6,1 and lower or 8,2 mmol/l and higher, are not eligible for Epo and thus not randomized. Patients in both strata will be randomized for three modalities: a cell saver (CS)(to wash, filter and reinfuse autologous shed blood) which is used intra- and postoperatively or a postoperative autologous reinfusion drainage system (D) only (to filter and reinfuse autologous shed blood) or a restrictive transfusion trigger only (controls).

Inclusion criteria: All orthopedic patients of 18 years and older being considered for a primary or revision total knee- (TKR) or total hip replacement (THR).

Outcome measures:

Primary outcome: number of allogeneic red blood cell (RBC) transfusions.

Secondary outcome: transfusion reactions, rehabilitation time, length of hospital stay (days), peri- and post-operative complications during hospitalization, quality of life, cost analysis

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: erythropoietin; Device: OrthoPAT; Device: OrthoPAT; Device: Post-operative drain device; Other: erythropoietin and cell saver; Other: Erythropoietin and OrthoPAT; Other: Erythropoietin and drain device

Detailed Description

Power/data analysis: In order to be able to detect a 75% reduction of allogeneic transfusions by Epo and a reduction of 30% by autologous (shed blood) transfusions (CS or D) with a power= 0.9 and an alpha= 0.05, inclusion of 2250 surgery patients (in a worst case scenario of high standard deviations) are required for intention-to-treat analysis.

Knee surgery patients are not randomized for cell saver (no intra-operative blood loss).

• Study Type: Interventional
• Enrollment (Actual): 2598
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands
      • Slotervaart Hospital
  • Zuid Holland
    • Gouda, Zuid Holland, Netherlands
      • Groene Hart Hospital
  • Zuid-Holland
    • Dordrecht, Zuid-Holland, Netherlands
      • Albert Schweitzer Hospital
    • Leiden, Zuid-Holland, Netherlands
      • LUMC

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:

• Orthopaedic patients of 18 years and older being scheduled for a primary or revision total knee (TKR) or total hip replacement (THR).

Exclusion Criteria:

• Patients who refuse homologous blood (e.g.Jehovah's witnesses),
• Patients with untreated hypertension (diastolic blood pressure > 95 mm Hg),
• Patients with a serious disorder of the coronary artery, peripheral arteries and/or carotid arteries,
• A recent myocardial infarction or CVA,
• Sickle cell anaemia patients,
• Malignancy in the operated area,
• Pregnancy,
• Unsuitability for peri-operative anticoagulation prophylaxis,
• Known allergy to erythropoietin,
• An infected wound bed,
• Revision of an infected prosthesis which is being treated with antibiotics, OR
• Patients with difficulty understanding the Dutch language (unable to give informed consent or patients who insufficiently control the Dutch language).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Erythropoietin	Drug: erythropoietin; weekly 40.000 IU s.c. for 4 weeks pre-operatively; Other Names: Eprex, Ortho-Biotech; Neorecormon, Roche
NO_INTERVENTION: Control arm
EXPERIMENTAL: cell saver	Device: OrthoPAT; for intra- and post-operative re-infusion of autologous wound blood; Other Names: OrthoPAT, Haemonetics; Device: OrthoPAT; For intra- and post-operative reinfusion of autologous blood; Other Names: OrthoPAT, Haemonetics
EXPERIMENTAL: drain	Device: Post-operative drain device; For post-operative re-infusion of unwashed wound blood; Other Names: Bellovac-ABT, Astra-Tech, The Netherlands; DONOR-drain, Van Straten Medical, The Netherlands
EXPERIMENTAL: Erythropoietin and cell saver	Other: erythropoietin and cell saver; weekly 40.000 IU s.c. for 4 weeks pre-operatively; use of cell saver includes intra- and post-operative drainage and reinfusion; Other Names: Eprex, Ortho-Biotech; Neorecormon, Roche; OrthoPAT, Haemonetics; Other: Erythropoietin and OrthoPAT; weekly 40.000 IU s.c. for 4 weeks pre-operatively; Other Names: Eprex, Ortho-Biotech; Neorecormon, Roche; OrthoPAT, Haemonetics
EXPERIMENTAL: Erythropoietin and drain	Other: Erythropoietin and drain device; weekly 40.000 IE s.c.for 4 weeks pre-operatively; drain use in post-operative period; Other Names: Eprex, Ortho-Biotech; Neorecormon, Roche; Bellovac-ABT, Astra-Tech; DONOR-drain, Van Straten Medical

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of allogeneic red blood cell (RBC) transfusions.	up to 3 months after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Peri- and post-operative complications during hospitalization	up to 3 months after surgery
Rehabilitation time	in hospital
Hb/Ht post-operative	at 14 days and 3 months after surgery
Quality of life	Up to 3 months after surgery
Transfusion reactions	up to 3 months after surgery
Harris hip / knee society score (for determination of the mobility of the operated joint)	pre-operative and after 3 months
Cost analysis	up to 3 months after surgery
Length of hospital stay	In hospital

Collaborators and Investigators

• Sponsor: Sanquin Research & Blood Bank Divisions
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; Roche BV Netherlands; Haemonetics Corporation
• Investigators: Principal Investigator: Rob Nelissen, MD, PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (ACTUAL): September 1, 2009
• Study Completion (ACTUAL): September 1, 2009

Study Registration Dates

• First Submitted: October 19, 2009
• First Submitted That Met QC Criteria: October 19, 2009
• First Posted (ESTIMATE): October 20, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): October 20, 2009
• Last Update Submitted That Met QC Criteria: October 19, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: hip replacement; knee replacement; Blood management; adults; randomized study; elective; Orthopedic surgery
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Hematinics; Epoetin Alfa
• Other Study ID Numbers: ISRCTN96327523; NTR303; ZonMW945-06-601; Sanquin PPOC-03-002