A Pilot Study of Hemin Therapy for Gastroparesis (Diabetes Mellitus)

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01206582
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Recordati Rare Diseases (Industry)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 55
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Gastroparesis; Diabetes Mellitus	Biological: Hemin; Biological: Albumin	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Hemin Therapy for Gastroparesis
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Hemin Panhematin®, Ovation Pharmaceuticals, Deerfield, Illinois (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	Biological: Hemin; 10 iv infusions for 8 weeks; Other Names: Panhematin®, (Ovation Pharmaceuticals, Deerfield, IL)
Placebo Comparator: Albumin 10 iv infusions for 8 weeks	Biological: Albumin; 10 iv infusions for 8 weeks; Other Names: Albumin (Human) 25% Solution manufactured by CSL Behring.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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.

2. 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.

3. Serum Creatinine [baseline, Day 4, Day 7, Day 56]

4. Prothrombin Time [baseline, Day 4, Day 7, Day 56]

5. Activated Partial Thromboplastin Time (APTT) [baseline, Day 4, Day 7, Day 56]

6. Hemoglobin [baseline, Day 4, Day 7, Day 56]

   Measured by complete blood count

7. Erythrocyte Count [baseline, Day 4, Day 7, Day 56]

   Measured by complete blood count

8. Leukocyte and Platelet Counts [baseline, Day 4, Day 7, Day 56]

   Measured by complete blood count

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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.

Exclusion Criteria:

• History of allergic reaction or significant sensitivity to Panhemantin ®

• Patients who have taken or used any investigational drug or device in the 30 days prior to screening

• Predominant symptoms of epigastric pain or rumination syndrome

• Structural cause for symptoms on recent endoscopy

• Patients with preexisting blood coagulation abnormalities

• Patients with previously documented renal impairment defined as above 150 mmol/L or 1.7 mg/dL serum creatinine

• Previous gastric or intestinal surgery - patients with enteral feeding tubes and/or venting/feeding gastrostomy will be eligible provided they can comply with study requirements. Tube feeding will be stopped 24 hours before the gastric emptying study

• Current use of narcotics, anticholinergic agents (e.g., hyoscyamine, belladonna), anticoagulants (e.g., warfarin) or erythromycin. Gastrointestinal prokinetic drugs (eg metoclopramide, or domperidone) may be continued at a stable dose throughout the study

• History of a pre-existing medical condition that, in the opinion of the investigator, will interfere with the participation in the study.

• History of venous thrombosis or hypercoagulable state

• Poor peripheral venous access, if central venous access is not available

• Uncontrolled active infection

• Any other condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study.

• Known intolerance or allergy to eggs

• Screening weight greater than 130 kg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55901

Sponsors and Collaborators

• Mayo Clinic
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Recordati Rare Diseases

Investigators

• Principal Investigator: Adil E Bharucha, MBBS, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Adil Bharucha, PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01206582
• Other Study ID Numbers: 09-000129; P01DK068055; UL1TR000135
• First Posted: Sep 22, 2010
• Last Update Posted: Feb 4, 2016
• Last Verified: Jan 1, 2016

• Additional relevant MeSH terms: Gastroparesis; Diabetes Mellitus

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled at Mayo Clinic in Rochester, Minnesota between Mayo 2010 and November 2013.

Arm/Group Title	Hemin	Albumin
Arm/Group Description	Panhematin®, Ovation Pharmaceuticals, Deerfield, Illinois (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	10 iv infusions for 8 weeks
Period Title: Overall Study
STARTED	11	9
COMPLETED	9	7
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Hemin	Albumin	Total
Arm/Group Description	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	10 iv infusions for 8 weeks	Total of all reporting groups
Overall Participants	11	9	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.9 (14.4)	35.2 (14.9)	41.1 (15.3)
Sex: Female, Male (Count of Participants)
Female	9 81.8%	9 100%	18 90%
Male	2 18.2%	0 0%	2 10%
Region of Enrollment (participants) [Number]
United States	11 100%	9 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
baseline (n=11, 8)	1.6 (0.3)	1.5 (0.1)
Day 3 (n=10, 8)	10.6 (2.3)	1.5 (0.3)
Day 7 (n=8, 8)	7.0 (2.1)	1.2 (0.2)
Day 56 (n=9, 4)	2.6 (0.8)	1.0 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hemin, Albumin
	Comments	Comparison for day 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Hemin, Albumin
	Comments	Comparison for day 7
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Venous Monocyte HO1 Activity
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
Baseline (n=10, 8)	38.5 (12.0)	42.1 (10.9)
Day 3 (n=9, 8)	373.9 (82.8)	48.1 (12.9)
Day 7 (n=8, 8)	126.2 (51.3)	36.1 (12.0)
Day 56 (n=8, 4)	30.1 (12.7)	60.1 (23.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hemin, Albumin
	Comments	Comparison for day 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments

3. Primary Outcome

Title	Gastric Emptying Half-time
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
Baseline (n=10, 9)	161.8 (6.7)	160.1 (16.3)
Day 3 (n=10, 9)	155.6 (9.1)	155.4 (16.5)
Day 7 (n=9, 8)	154.0 (6.5)	155.4 (15.0)
Day 56 (n=9, 6)	161.2 (6.2)	153.4 (16.4)

4. Secondary Outcome

Title	Gastrointestinal Symptoms
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	9	9
Baseline GCSI total score (n= 9, 9)	3.1 (0.3)	3.3 (0.1)
8 weeks GCSI total score (n=9, 7)	1.4 (0.3)	1.9 (0.5)
Baseline nausea/vomiting subscore (n=9, 9)	2.9 (0.6)	3.2 (0.4)
8 weeks nausea/vomiting subscore (n=9, 7)	1.3 (0.4)	1.3 (0.4)
Baseline fullness/early satiety subscore (n= 9, 9)	3.8 (0.3)	3.4 (0.3)
8 weeks fullness/early satiety subscore (n=9, 7)	1.9 (0.4)	2.1 (0.5)
Baseline bloating subscore (n=9, 9)	2.6 (0.5)	3.4 (0.4)
8 weeks bloating subscore (n=9, 7)	1.0 (0.3)	2.4 (0.7)
Baseline upper abdominal pain score (n= 9, 9)	3.7 (0.4)	2.8 (0.6)
8 weeks upper abdominal pain score (n=9, 7)	1.4 (0.4)	1.7 (0.6)
Baseline lower abdominal pain subscore (n=9, 9)	2.6 (0.4)	1.9 (0.4)
8 weeks lower abdominal pain subscore (n=9, 7)	1.3 (0.4)	1.4 (0.5)
Baseline heartburn/regurgitation subscore (n=9, 9)	2.0 (0.4)	1.8 (0.4)
8 weeks heartburn/regurgitation subscore (n=9, 7)	1.0 (0.4)	0.9 (0.5)
Baseline FDA NVFP composite subscore (n=9, 9)	3.4 (0.4)	3.3 (0.2)
8 weeks FDA NVFP composite subscore (n=9, 7)	1.5 (0.4)	1.7 (0.4)

5. Secondary Outcome

Title	Autonomic Functions
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
CASS vagal score - baseline (n=9, 8)	1.6 (0.5)	1.7 (1.1)
CASS vagal score - day 56 (n=9, 8)	1.2 (0.4)	1.9 (0.4)
Cass adrenergic score - baseline (n=5, 6)	1.0 (0.5)	1.6 (1.3)
Cass adrenergic score - day 56 (n=5, 6)	0.6 (0.4)	1.2 (0.6)

6. Secondary Outcome

Title	Serum Creatinine
Time Frame	baseline, Day 4, Day 7, Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
Baseline	1.0 (0.1)	0.7 (0.1)
Day 4	1.0 (0.1)	0.6 (0.1)
Day 7	0.9 (0.1)	0.7 (0.1)
Day 56	0.8 (0.1)	0.7 (0.1)

7. Secondary Outcome

Title	Prothrombin Time
Time Frame	baseline, Day 4, Day 7, Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
Baseline	1.0 (0.1)	0.9 (0.1)
Day 4	1.0 (0.1)	1.0 (0.1)
Day 7	1.0 (0.1)	1.0 (0.1)
Day 56	1.0 (0.1)	1.0 (0.1)

8. Secondary Outcome

Title	Activated Partial Thromboplastin Time (APTT)
Time Frame	baseline, Day 4, Day 7, Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
Baseline	32 (1.8)	32 (0.9)
Day 4	33 (1.0)	31 (1.5)
Day 7	30 (1.3)	31 (1.4)
Day 56	30 (1.2)	32 (1.3)

9. Secondary Outcome

Title	Hemoglobin
Description	Measured by complete blood count
Time Frame	baseline, Day 4, Day 7, Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
Baseline	12.1 (0.4)	12.4 (0.5)
Day 4	11.5 (0.5)	11.5 (0.5)
Day 7	11.6 (0.6)	11.2 (0.4)
Day 56	11.3 (0.6)	11.2 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hemin, Albumin
	Comments	Comparison for Day 7
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANCOVA
	Comments

10. Secondary Outcome

Title	Erythrocyte Count
Description	Measured by complete blood count
Time Frame	baseline, Day 4, Day 7, Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
Baseline	4.1 (0.1)	4.4 (0.1)
Day 4	4.0 (0.1)	4.1 (0.1)
Day 7	4.0 (0.2)	4.0 (0.1)
Day 56	4.0 (0.2)	4.0 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hemin, Albumin
	Comments	Comparison for Day 7
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANCOVA
	Comments

11. Secondary Outcome

Title	Leukocyte and Platelet Counts
Description	Measured by complete blood count
Time Frame	baseline, Day 4, Day 7, Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hemin	Albumin
Arm/Group Description	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	10 iv infusions for 8 weeks
Measure Participants	11	9
Leukocytes Baseline	7.0 (0.6)	6.0 (0.5)
Leukocytes Day 4	7.0 (0.5)	6.2 (0.6)
Leukocytes Day 7	7.2 (0.6)	6.8 (1.2)
Leukocytes Day 56	7.3 (0.5)	6.5 (0.8)
Platelets Baseline	248 (18)	266 (26)
Platelets Day 4	194 (14)	246 (21)
Platelets Day 7	201 (15)	248 (26)
Platelets Day 56	212 (12)	251 (41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hemin, Albumin
	Comments	Comparison for Platelets on Day 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Hemin		Albumin
Arm/Group Description	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		10 iv infusions for 8 weeks
All Cause Mortality
	Hemin		Albumin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Hemin		Albumin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Hemin		Albumin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/11 (45.5%)		7/9 (77.8%)
Gastrointestinal disorders
Nausea	1/11 (9.1%)	1	3/9 (33.3%)	3
General disorders
Headache	2/11 (18.2%)	2	3/9 (33.3%)	3
Dizziness or light headedness	2/11 (18.2%)	2	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Maculopapular rash	0/11 (0%)	0	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

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.