Diabetes Mellitus, Gastroparesis
Conditions
Brief summary
This study is designed to learn if hemin can increase the production of heme oxygenase 1 and improve gastric (stomach) emptying and symptoms in diabetic patients with slow gastric emptying (gastroparesis).
Detailed description
Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase 1 (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying in diabetic non-obese diabetic mice. HO1 is an enzyme which protects cells from physical, chemical, and biologic stress. In mice with diabetes and slow gastric emptying, hemin increases HO-1 activity and improves gastric emptying. Hemin is produced from red blood cells and is approved by the Food and Drug Administration for treating acute porphyria, which is an inherited condition caused by an enzyme deficiency. Hemin is not approved by the Food and Drug Administration for treating gastroparesis. In this study subjects were randomized to intravenous hemin, prepared in albumin, or albumin alone. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, gastric emptying with 13\^C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks.
Interventions
BIOLOGICALHemin
10 iv infusions for 8 weeks
BIOLOGICALAlbumin
10 iv infusions for 8 weeks
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
RECORDATI GROUP
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Where relevant (i.e., for ensuring safety), the inclusion and
Exclusion criteria
are similar to those in a recently completed trial of hemin therapy for myelodysplastic syndrome at Rush University, Chicago (http://clinicaltrials.gov/ct2/show/NCT00467610). * Upper gastrointestinal symptoms which satisfy criteria for postprandial distress syndrome or vomiting for the last 3 months with symptom onset at least 6 months prior to diagnosis * At least moderately severe symptoms as manifest by a total symptom score of 2.5 or higher on the Gastroparesis Cardinal Symptom Index (GCSI)21 * Delayed gastric emptying (i.e, \< 40% emptying at 2 and/or \< 90% emptying at 4 hours by scintigraphy) * No structural cause for symptoms by endoscopy within the past 12 months * Patient must have a platelet counts \> 50,000/microliters and absolute neutrophil counts (ANC) \>500/microliters. * Patient must have adequate hepatic and renal functions, defined as serum bilirubin, serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamate pyruvate transaminase (SGPT) ≤ 2 times the upper limit of normal (ULN), and creatinine ≤ 1.5 times the ULN. * Able to provide written informed consent before participating in the study If female: * Either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or if of childbearing potential, must comply with an effective method of birth control acceptable to the investigator during the study (oral contraceptives, Depo-Provera, intra-uterine device or barrier methods) * Patient is not breastfeeding. * Patient of childbearing potential must have a negative urine or serum pregnancy test during the screening period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | baseline, day 3, day 7, day 56 | HO1 protein concentration levels in plasma were assessed with a HO1 (human) enzyme-linked immunosorbent assay (ELISA) kit. |
| Venous Monocyte HO1 Activity | baseline, Day 3, Day 7, Day 56 | HO1 activity in white blood cells was measured by an assay that measures bilirubin production as a marker of HO1 activity. |
| Gastric Emptying Half-time | baseline, day 3, day 7, day 56 | The time for half of the ingested solids or liquids to leave the stomach. Gastric emptying was assessed with \^13C Spirulina Breath Test. After an overnight fast, subjects consumed the test meal containing \^13C Spirulina. Breath samples were collected in duplicate glass tube using a straw to blow into the bottom of the tube to displace contained air. The \^13CO\_2 content of the breath was determined by AB Diagnostics. The provide of \^13CO\_2 excretion is used to estimate the half-time of gastric emptying. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prothrombin Time | baseline, Day 4, Day 7, Day 56 | — |
| Activated Partial Thromboplastin Time (APTT) | baseline, Day 4, Day 7, Day 56 | — |
| Gastrointestinal Symptoms | baseline, 8 weeks | Subjects recorded their GI symptoms every day in the validated Gastroparesis Cardinal Symptom Index (GCSI) - Daily Diary. For each subject, the daily GCSI data were averaged per week. Components coded 0 (no symptoms) to 5 (very severe). GCSI total score is the average of 9 components from the nausea/vomiting, fullness/early satiety, and bloating subscores. These individual subscores are averages of 3,4, and 2 components, respectively. Subscores for upper and lower abdominal pain, heartburn/regurgitation and FDA nausea, vomiting, fullness, and pain (NVFP) composite are averages of 2, 2, 7, and 4 components, respectively. |
| Erythrocyte Count | baseline, Day 4, Day 7, Day 56 | Measured by complete blood count |
| Leukocyte and Platelet Counts | baseline, Day 4, Day 7, Day 56 | Measured by complete blood count |
| Hemoglobin | baseline, Day 4, Day 7, Day 56 | Measured by complete blood count |
| Autonomic Functions | baseline, Day 56 | Subjects completed a standardized autonomic symptom questionnaire, the Composite Autonomic Severity Score (CASS) which consists of 2 subscores: cardiovagal (CASS-vag; 0-3) and adrenergic (CASS-adr;0-3), where 0, 1, 2, 3 represent non, mild, moderate, and severe dysfunction, respectively. |
| Serum Creatinine | baseline, Day 4, Day 7, Day 56 | — |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled at Mayo Clinic in Rochester, Minnesota between Mayo 2010 and November 2013.
Participants by arm
| Arm | Count |
|---|---|
| Hemin Panhematin®, Ovation Pharmaceuticals, Deerfield, IL. Hemin was diluted in 25% albumin to obtain a concentration of 2.4 mg/mL and administered at a dose of 1.25 mL/Kg and at a rate of 60 mL/hour. 10 iv infusions for 8 weeks | 11 |
| Albumin 10 iv infusions for 8 weeks | 9 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued intervention before week 8 | 1 | 2 |
| Overall Study | Withdrew prior to study | 1 | 0 |
Baseline characteristics
| Characteristic | Hemin | Albumin | Total |
|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 14.4 | 35.2 years STANDARD_DEVIATION 14.9 | 41.1 years STANDARD_DEVIATION 15.3 |
| Region of Enrollment United States | 11 participants | 9 participants | 20 participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 11 | 7 / 9 |
| serious Total, serious adverse events | 0 / 11 | 0 / 9 |
Outcome results
Primary
Gastric Emptying Half-time
The time for half of the ingested solids or liquids to leave the stomach. Gastric emptying was assessed with \^13C Spirulina Breath Test. After an overnight fast, subjects consumed the test meal containing \^13C Spirulina. Breath samples were collected in duplicate glass tube using a straw to blow into the bottom of the tube to displace contained air. The \^13CO\_2 content of the breath was determined by AB Diagnostics. The provide of \^13CO\_2 excretion is used to estimate the half-time of gastric emptying.
Time frame: baseline, day 3, day 7, day 56
Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Gastric Emptying Half-time | Baseline (n=10, 9) | 161.8 minutes | Standard Error 6.7 |
| Hemin | Gastric Emptying Half-time | Day 3 (n=10, 9) | 155.6 minutes | Standard Error 9.1 |
| Hemin | Gastric Emptying Half-time | Day 7 (n=9, 8) | 154.0 minutes | Standard Error 6.5 |
| Hemin | Gastric Emptying Half-time | Day 56 (n=9, 6) | 161.2 minutes | Standard Error 6.2 |
| Albumin | Gastric Emptying Half-time | Day 56 (n=9, 6) | 153.4 minutes | Standard Error 16.4 |
| Albumin | Gastric Emptying Half-time | Baseline (n=10, 9) | 160.1 minutes | Standard Error 16.3 |
| Albumin | Gastric Emptying Half-time | Day 7 (n=9, 8) | 155.4 minutes | Standard Error 15 |
| Albumin | Gastric Emptying Half-time | Day 3 (n=10, 9) | 155.4 minutes | Standard Error 16.5 |
Primary
Venous Monocyte HO1 Activity
HO1 activity in white blood cells was measured by an assay that measures bilirubin production as a marker of HO1 activity.
Time frame: baseline, Day 3, Day 7, Day 56
Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Venous Monocyte HO1 Activity | Baseline (n=10, 8) | 38.5 pmol bilirubin/mg/h | Standard Error 12 |
| Hemin | Venous Monocyte HO1 Activity | Day 7 (n=8, 8) | 126.2 pmol bilirubin/mg/h | Standard Error 51.3 |
| Hemin | Venous Monocyte HO1 Activity | Day 3 (n=9, 8) | 373.9 pmol bilirubin/mg/h | Standard Error 82.8 |
| Hemin | Venous Monocyte HO1 Activity | Day 56 (n=8, 4) | 30.1 pmol bilirubin/mg/h | Standard Error 12.7 |
| Albumin | Venous Monocyte HO1 Activity | Day 3 (n=9, 8) | 48.1 pmol bilirubin/mg/h | Standard Error 12.9 |
| Albumin | Venous Monocyte HO1 Activity | Baseline (n=10, 8) | 42.1 pmol bilirubin/mg/h | Standard Error 10.9 |
| Albumin | Venous Monocyte HO1 Activity | Day 56 (n=8, 4) | 60.1 pmol bilirubin/mg/h | Standard Error 23 |
| Albumin | Venous Monocyte HO1 Activity | Day 7 (n=8, 8) | 36.1 pmol bilirubin/mg/h | Standard Error 12 |
Comparison: Comparison for day 3p-value: 0.0003ANCOVA
Primary
Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration
HO1 protein concentration levels in plasma were assessed with a HO1 (human) enzyme-linked immunosorbent assay (ELISA) kit.
Time frame: baseline, day 3, day 7, day 56
Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | baseline (n=11, 8) | 1.6 ng/mL | Standard Error 0.3 |
| Hemin | Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | Day 3 (n=10, 8) | 10.6 ng/mL | Standard Error 2.3 |
| Hemin | Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | Day 7 (n=8, 8) | 7.0 ng/mL | Standard Error 2.1 |
| Hemin | Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | Day 56 (n=9, 4) | 2.6 ng/mL | Standard Error 0.8 |
| Albumin | Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | Day 56 (n=9, 4) | 1.0 ng/mL | Standard Error 0.1 |
| Albumin | Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | baseline (n=11, 8) | 1.5 ng/mL | Standard Error 0.1 |
| Albumin | Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | Day 7 (n=8, 8) | 1.2 ng/mL | Standard Error 0.2 |
| Albumin | Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration | Day 3 (n=10, 8) | 1.5 ng/mL | Standard Error 0.3 |
Comparison: Comparison for day 3p-value: 0.0002ANCOVA
Comparison: Comparison for day 7p-value: 0.008ANCOVA
Secondary
Activated Partial Thromboplastin Time (APTT)
Time frame: baseline, Day 4, Day 7, Day 56
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Activated Partial Thromboplastin Time (APTT) | Baseline | 32 Seconds | Standard Error 1.8 |
| Hemin | Activated Partial Thromboplastin Time (APTT) | Day 4 | 33 Seconds | Standard Error 1 |
| Hemin | Activated Partial Thromboplastin Time (APTT) | Day 7 | 30 Seconds | Standard Error 1.3 |
| Hemin | Activated Partial Thromboplastin Time (APTT) | Day 56 | 30 Seconds | Standard Error 1.2 |
| Albumin | Activated Partial Thromboplastin Time (APTT) | Day 56 | 32 Seconds | Standard Error 1.3 |
| Albumin | Activated Partial Thromboplastin Time (APTT) | Baseline | 32 Seconds | Standard Error 0.9 |
| Albumin | Activated Partial Thromboplastin Time (APTT) | Day 7 | 31 Seconds | Standard Error 1.4 |
| Albumin | Activated Partial Thromboplastin Time (APTT) | Day 4 | 31 Seconds | Standard Error 1.5 |
Secondary
Autonomic Functions
Subjects completed a standardized autonomic symptom questionnaire, the Composite Autonomic Severity Score (CASS) which consists of 2 subscores: cardiovagal (CASS-vag; 0-3) and adrenergic (CASS-adr;0-3), where 0, 1, 2, 3 represent non, mild, moderate, and severe dysfunction, respectively.
Time frame: baseline, Day 56
Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Autonomic Functions | CASS vagal score - baseline (n=9, 8) | 1.6 units on a scale | Standard Error 0.5 |
| Hemin | Autonomic Functions | CASS vagal score - day 56 (n=9, 8) | 1.2 units on a scale | Standard Error 0.4 |
| Hemin | Autonomic Functions | Cass adrenergic score - baseline (n=5, 6) | 1.0 units on a scale | Standard Error 0.5 |
| Hemin | Autonomic Functions | Cass adrenergic score - day 56 (n=5, 6) | 0.6 units on a scale | Standard Error 0.4 |
| Albumin | Autonomic Functions | Cass adrenergic score - day 56 (n=5, 6) | 1.2 units on a scale | Standard Error 0.6 |
| Albumin | Autonomic Functions | CASS vagal score - baseline (n=9, 8) | 1.7 units on a scale | Standard Error 1.1 |
| Albumin | Autonomic Functions | Cass adrenergic score - baseline (n=5, 6) | 1.6 units on a scale | Standard Error 1.3 |
| Albumin | Autonomic Functions | CASS vagal score - day 56 (n=9, 8) | 1.9 units on a scale | Standard Error 0.4 |
Secondary
Erythrocyte Count
Measured by complete blood count
Time frame: baseline, Day 4, Day 7, Day 56
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Erythrocyte Count | Baseline | 4.1 number x 10^12 erythrocytes/L | Standard Error 0.1 |
| Hemin | Erythrocyte Count | Day 4 | 4.0 number x 10^12 erythrocytes/L | Standard Error 0.1 |
| Hemin | Erythrocyte Count | Day 7 | 4.0 number x 10^12 erythrocytes/L | Standard Error 0.2 |
| Hemin | Erythrocyte Count | Day 56 | 4.0 number x 10^12 erythrocytes/L | Standard Error 0.2 |
| Albumin | Erythrocyte Count | Day 56 | 4.0 number x 10^12 erythrocytes/L | Standard Error 0.1 |
| Albumin | Erythrocyte Count | Baseline | 4.4 number x 10^12 erythrocytes/L | Standard Error 0.1 |
| Albumin | Erythrocyte Count | Day 7 | 4.0 number x 10^12 erythrocytes/L | Standard Error 0.1 |
| Albumin | Erythrocyte Count | Day 4 | 4.1 number x 10^12 erythrocytes/L | Standard Error 0.1 |
Comparison: Comparison for Day 7p-value: <0.05ANCOVA
Secondary
Gastrointestinal Symptoms
Subjects recorded their GI symptoms every day in the validated Gastroparesis Cardinal Symptom Index (GCSI) - Daily Diary. For each subject, the daily GCSI data were averaged per week. Components coded 0 (no symptoms) to 5 (very severe). GCSI total score is the average of 9 components from the nausea/vomiting, fullness/early satiety, and bloating subscores. These individual subscores are averages of 3,4, and 2 components, respectively. Subscores for upper and lower abdominal pain, heartburn/regurgitation and FDA nausea, vomiting, fullness, and pain (NVFP) composite are averages of 2, 2, 7, and 4 components, respectively.
Time frame: baseline, 8 weeks
Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Gastrointestinal Symptoms | Baseline GCSI total score (n= 9, 9) | 3.1 units on a scale | Standard Error 0.3 |
| Hemin | Gastrointestinal Symptoms | 8 weeks GCSI total score (n=9, 7) | 1.4 units on a scale | Standard Error 0.3 |
| Hemin | Gastrointestinal Symptoms | Baseline nausea/vomiting subscore (n=9, 9) | 2.9 units on a scale | Standard Error 0.6 |
| Hemin | Gastrointestinal Symptoms | 8 weeks nausea/vomiting subscore (n=9, 7) | 1.3 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | Baseline fullness/early satiety subscore (n= 9, 9) | 3.8 units on a scale | Standard Error 0.3 |
| Hemin | Gastrointestinal Symptoms | 8 weeks fullness/early satiety subscore (n=9, 7) | 1.9 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | Baseline bloating subscore (n=9, 9) | 2.6 units on a scale | Standard Error 0.5 |
| Hemin | Gastrointestinal Symptoms | 8 weeks bloating subscore (n=9, 7) | 1.0 units on a scale | Standard Error 0.3 |
| Hemin | Gastrointestinal Symptoms | Baseline upper abdominal pain score (n= 9, 9) | 3.7 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | 8 weeks upper abdominal pain score (n=9, 7) | 1.4 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | Baseline lower abdominal pain subscore (n=9, 9) | 2.6 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | 8 weeks lower abdominal pain subscore (n=9, 7) | 1.3 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | Baseline heartburn/regurgitation subscore (n=9, 9) | 2.0 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | 8 weeks heartburn/regurgitation subscore (n=9, 7) | 1.0 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | Baseline FDA NVFP composite subscore (n=9, 9) | 3.4 units on a scale | Standard Error 0.4 |
| Hemin | Gastrointestinal Symptoms | 8 weeks FDA NVFP composite subscore (n=9, 7) | 1.5 units on a scale | Standard Error 0.4 |
| Albumin | Gastrointestinal Symptoms | 8 weeks FDA NVFP composite subscore (n=9, 7) | 1.7 units on a scale | Standard Error 0.4 |
| Albumin | Gastrointestinal Symptoms | Baseline GCSI total score (n= 9, 9) | 3.3 units on a scale | Standard Error 0.1 |
| Albumin | Gastrointestinal Symptoms | Baseline upper abdominal pain score (n= 9, 9) | 2.8 units on a scale | Standard Error 0.6 |
| Albumin | Gastrointestinal Symptoms | 8 weeks GCSI total score (n=9, 7) | 1.9 units on a scale | Standard Error 0.5 |
| Albumin | Gastrointestinal Symptoms | Baseline heartburn/regurgitation subscore (n=9, 9) | 1.8 units on a scale | Standard Error 0.4 |
| Albumin | Gastrointestinal Symptoms | Baseline nausea/vomiting subscore (n=9, 9) | 3.2 units on a scale | Standard Error 0.4 |
| Albumin | Gastrointestinal Symptoms | 8 weeks upper abdominal pain score (n=9, 7) | 1.7 units on a scale | Standard Error 0.6 |
| Albumin | Gastrointestinal Symptoms | 8 weeks nausea/vomiting subscore (n=9, 7) | 1.3 units on a scale | Standard Error 0.4 |
| Albumin | Gastrointestinal Symptoms | Baseline FDA NVFP composite subscore (n=9, 9) | 3.3 units on a scale | Standard Error 0.2 |
| Albumin | Gastrointestinal Symptoms | Baseline fullness/early satiety subscore (n= 9, 9) | 3.4 units on a scale | Standard Error 0.3 |
| Albumin | Gastrointestinal Symptoms | Baseline lower abdominal pain subscore (n=9, 9) | 1.9 units on a scale | Standard Error 0.4 |
| Albumin | Gastrointestinal Symptoms | 8 weeks fullness/early satiety subscore (n=9, 7) | 2.1 units on a scale | Standard Error 0.5 |
| Albumin | Gastrointestinal Symptoms | 8 weeks heartburn/regurgitation subscore (n=9, 7) | 0.9 units on a scale | Standard Error 0.5 |
| Albumin | Gastrointestinal Symptoms | Baseline bloating subscore (n=9, 9) | 3.4 units on a scale | Standard Error 0.4 |
| Albumin | Gastrointestinal Symptoms | 8 weeks lower abdominal pain subscore (n=9, 7) | 1.4 units on a scale | Standard Error 0.5 |
| Albumin | Gastrointestinal Symptoms | 8 weeks bloating subscore (n=9, 7) | 2.4 units on a scale | Standard Error 0.7 |
Secondary
Hemoglobin
Measured by complete blood count
Time frame: baseline, Day 4, Day 7, Day 56
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Hemoglobin | Baseline | 12.1 g/dL | Standard Error 0.4 |
| Hemin | Hemoglobin | Day 4 | 11.5 g/dL | Standard Error 0.5 |
| Hemin | Hemoglobin | Day 7 | 11.6 g/dL | Standard Error 0.6 |
| Hemin | Hemoglobin | Day 56 | 11.3 g/dL | Standard Error 0.6 |
| Albumin | Hemoglobin | Day 56 | 11.2 g/dL | Standard Error 0.3 |
| Albumin | Hemoglobin | Baseline | 12.4 g/dL | Standard Error 0.5 |
| Albumin | Hemoglobin | Day 7 | 11.2 g/dL | Standard Error 0.4 |
| Albumin | Hemoglobin | Day 4 | 11.5 g/dL | Standard Error 0.5 |
Comparison: Comparison for Day 7p-value: <0.05ANCOVA
Secondary
Leukocyte and Platelet Counts
Measured by complete blood count
Time frame: baseline, Day 4, Day 7, Day 56
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Leukocyte and Platelet Counts | Platelets Day 4 | 194 number x 10^9 cells/L | Standard Error 14 |
| Hemin | Leukocyte and Platelet Counts | Leukocytes Baseline | 7.0 number x 10^9 cells/L | Standard Error 0.6 |
| Hemin | Leukocyte and Platelet Counts | Leukocytes Day 4 | 7.0 number x 10^9 cells/L | Standard Error 0.5 |
| Hemin | Leukocyte and Platelet Counts | Leukocytes Day 7 | 7.2 number x 10^9 cells/L | Standard Error 0.6 |
| Hemin | Leukocyte and Platelet Counts | Leukocytes Day 56 | 7.3 number x 10^9 cells/L | Standard Error 0.5 |
| Hemin | Leukocyte and Platelet Counts | Platelets Baseline | 248 number x 10^9 cells/L | Standard Error 18 |
| Hemin | Leukocyte and Platelet Counts | Platelets Day 7 | 201 number x 10^9 cells/L | Standard Error 15 |
| Hemin | Leukocyte and Platelet Counts | Platelets Day 56 | 212 number x 10^9 cells/L | Standard Error 12 |
| Albumin | Leukocyte and Platelet Counts | Platelets Day 56 | 251 number x 10^9 cells/L | Standard Error 41 |
| Albumin | Leukocyte and Platelet Counts | Platelets Day 4 | 246 number x 10^9 cells/L | Standard Error 21 |
| Albumin | Leukocyte and Platelet Counts | Leukocytes Day 56 | 6.5 number x 10^9 cells/L | Standard Error 0.8 |
| Albumin | Leukocyte and Platelet Counts | Leukocytes Baseline | 6.0 number x 10^9 cells/L | Standard Error 0.5 |
| Albumin | Leukocyte and Platelet Counts | Platelets Day 7 | 248 number x 10^9 cells/L | Standard Error 26 |
| Albumin | Leukocyte and Platelet Counts | Leukocytes Day 4 | 6.2 number x 10^9 cells/L | Standard Error 0.6 |
| Albumin | Leukocyte and Platelet Counts | Platelets Baseline | 266 number x 10^9 cells/L | Standard Error 26 |
| Albumin | Leukocyte and Platelet Counts | Leukocytes Day 7 | 6.8 number x 10^9 cells/L | Standard Error 1.2 |
Comparison: Comparison for Platelets on Day 4p-value: 0.01ANCOVA
Secondary
Prothrombin Time
Time frame: baseline, Day 4, Day 7, Day 56
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Prothrombin Time | Baseline | 1.0 International Normalized Ratio (INR) | Standard Error 0.1 |
| Hemin | Prothrombin Time | Day 4 | 1.0 International Normalized Ratio (INR) | Standard Error 0.1 |
| Hemin | Prothrombin Time | Day 7 | 1.0 International Normalized Ratio (INR) | Standard Error 0.1 |
| Hemin | Prothrombin Time | Day 56 | 1.0 International Normalized Ratio (INR) | Standard Error 0.1 |
| Albumin | Prothrombin Time | Day 56 | 1.0 International Normalized Ratio (INR) | Standard Error 0.1 |
| Albumin | Prothrombin Time | Baseline | 0.9 International Normalized Ratio (INR) | Standard Error 0.1 |
| Albumin | Prothrombin Time | Day 7 | 1.0 International Normalized Ratio (INR) | Standard Error 0.1 |
| Albumin | Prothrombin Time | Day 4 | 1.0 International Normalized Ratio (INR) | Standard Error 0.1 |
Secondary
Serum Creatinine
Time frame: baseline, Day 4, Day 7, Day 56
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hemin | Serum Creatinine | Baseline | 1.0 mg/dL | Standard Error 0.1 |
| Hemin | Serum Creatinine | Day 56 | 0.8 mg/dL | Standard Error 0.1 |
| Hemin | Serum Creatinine | Day 7 | 0.9 mg/dL | Standard Error 0.1 |
| Hemin | Serum Creatinine | Day 4 | 1.0 mg/dL | Standard Error 0.1 |
| Albumin | Serum Creatinine | Day 4 | 0.6 mg/dL | Standard Error 0.1 |
| Albumin | Serum Creatinine | Day 7 | 0.7 mg/dL | Standard Error 0.1 |
| Albumin | Serum Creatinine | Baseline | 0.7 mg/dL | Standard Error 0.1 |
| Albumin | Serum Creatinine | Day 56 | 0.7 mg/dL | Standard Error 0.1 |