Approach to Clinical Trial Considering Medical Ethics and Efficacy for HbV, Liposome Encapsulated Hemoglobin Vesicle

Figures & data

Table 1 Physiochemical activity for efficacy

Oxygen Transport Function

Amount of Hb in the Vesicle

Oxygen Dissociation Curve (P50)

Conversion Rate from Hb to MetHb

Dispersibility of Vesicle in Medium

Size of Vesicle

Viscosity of HbV Solution

Homogeneity & Stability of the Vesicles in the Solution & Blood

pH of the Solution

Table 2 Clinical efficacy

Oxygen Supply to Tissue

Pulmonary Oxygenation (at FIO2 0.2–0.4)

Oxygen Release at Tissues

Conversion Rate from Hb to MetHb

Normal Cardiac Output

Maintenance of the Circulating Blood Volume

Retention Rate of HbV in the Circulation

Table 3 Safety of HbV solution

Clinical assessment
Psychological Function & Behavior	Nervous Function
Tendon & Muscle Function	Heart & Circulatory Function
Respiratory & Gas Exchange Function	Hepatic Function
Body Fluid Buffering Capacity	Serum Electrolyte Compositions
Renal Function	Digestive Function
Hemostatic & Fibrinolytic Function	Hematopoietic Function
Endocrine Functions	Defensive & Immune System
Reproductive Function	Teratogenicity
Tumorgenicity	Interaction with Drugs Commonly Used

Table 4 Consideration on medical ethics for clinical trial

Clinical trials should be done as treatment or therapy for patients

The treatment or therapy in clinical trials should be equivalent or superior to conventional treatment or therapy

Clinical trials must be performed with certain and proper informed consent

Table 5 Selection of subjects for the clinical trial regarding reception of informed consent

Sufficient Reason for Use of Artificial Blood

(1) without Adverse associated with Ordinary Blood Transfusion

(2) with Oxygen Carrying Property not for Plasma Substitutes

(3) Sufficient Interval between Finding Subject and Operation for Explain & Understanding Protocol and Receiving Consent

Indication for Alternative Transfusion with HbV: Acute Anemia which the HbV could be used for matched to its optimum properties

Table 6 First selection for clinical trial

Replacement for Surgical Blood Loss with 15–20 ml/kg

Hemodilutional Autologous Transfusion

Substitute for Blood Transfusion for Emergent Surgery without Proper Blood prepared

Substitute for Blood Transfusion for Unexpected Bleeding during Operation

Transfusion for Patient with Uncommon Blood Type or with Refusal of Blood Transfusion

Limited for Blood Loss of 15–20 ml/kg during the Clinical Trial but not for Clinical Use in the Future

Table 7 No program projected in clinical trials for new artificial blood

Post-traumatic Hypovolemia

Hemorrhagic Shock

Myocardial & Cerebral Ischemia due to Stenosis

Supplemental Treatment for Idiopathic Anemia

Priming for Extracorporeal Circuit

Superoxygenation for Malignant Neoplasma

Liquid Ventilation

Organ Perfusion & Preservation for Transplation

Table 8 Physiological parameters measured in the clinical trial

Arterial Blood Pressure	Arterial O2 Partial Pressure
Right Atrial Mean Pressure	Arterial CO2 Partial Pressure
Pulmonary Artery Blood Pressure^*	Arterial pH
Heart Rate	Arterial Lactate Level
Cardiac Output^*	Arterial Blood Hb, Hct & HbVcrit
ECG	Mixed Venous O2 Partial Pressure
Urine Volume	Mixed Venous O2 Saturation
Routine Urine Analysis	AV O2 Content Difference (calculation)
Routine Blood Chemical Analysis	O2 Consumption (calculation)^*

*If Swan Ganz Catheter could be allowed to be used.

Figure 1

Figure 2

Table 9 Social needs for artificial blood

Disaster Use ...... Long–term Shelf Storage

Emergent Use ...... Before Arrival of Matched or O(−) Blood

Shortage of Blood for Transfusion

Recycle Use of Hemoglobin from Donated Blood

Application as Universal Blood

Evasion from Transfusion Complications & Human Error

Transfusion for Patients with Uncommon Blood Type or with Refusal of Donated Blood