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| ID | Type | Description | Link |
|---|---|---|---|
| N01HD43386-7-0-1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Stanford University | OTHER |
| Duke University | OTHER |
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Sodium nitroprusside (SNP) has been approved for control of blood pressure in adults, yet there are no controlled studies in children. The purpose of this study is to determine the efficacy and safety of sodium nitroprusside in children who will be having surgery, and who require blood pressure lowering in order to decrease the amount of blood loss during their surgery.
The trial is a multicenter randomized, double-blind, parallel group, dose-ranging, effect-controlled study examining the effects of sodium nitroprusside in pediatric subjects requiring relative hypotension during a surgical or medical procedure. The goal is to establish the starting and maximum infusion rates that afford optimum blood pressure control in children and a safe dosing regimen in children. The objective is to describe the relationship between the infusion rate of nitroprusside and changes in blood pressure.
The specific aims of this trial are:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.3 mcg/kg/min | Active Comparator | Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons. |
|
| 1 mcg/kg/min | Active Comparator | Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons. |
|
| 2 mcg/kg/min | Active Comparator | Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nitroprusside | Drug | Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS (Interactive Voice Response System). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean Arterial Pressure (MAP) From the Baseline MAP | From the Baseline MAP until the end of the blinded phase; scheduled for 30 min | Approximately 30 minutes |
| Overall Summary of Tolerability/Adverse Events (AEs) for ITT Safety Population | Treatment-emergent AEs (TEAEs) were defined as an AE experienced by the patient that was either first observed after the initiation of study drug (blinded or open-label) or represented an exacerbation (usually in severity) of a pre existing condition observed prior to treatment. Subjects will be followed for 30 days after discontinuation of study drug. The occurrence of Serious Adverse Events (SAEs) will be monitored for 30 days. | 30 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline MAP Nitroprusside Infusion During the Blinded Infusion; | Change From Baseline in MAP (mmHg) After 20 and 25 Minutes Double-Blind Infusion (Overall) for ITT Efficacy Evaluable Population. | 25 minutes |
| Infusion Rate of Sodium Nitroprusside That Reduces MAP to a Predetermined Clinically Meaningful Target Value +/- 10%; |
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Inclusion Criteria:
Study subjects must meet all of the following criteria:
Exclusion Criteria:
Subjects will be excluded if any of the following criteria exist:
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| Name | Affiliation | Role |
|---|---|---|
| Gregory Hammer, MD | Stanford University | Principal Investigator |
| Scott Schulman, MD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94305-5401 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26217225 | Derived | Drover DR, Hammer GB, Barrett JS, Cohane CA, Reece T, Zajicek A, Schulman SR. Evaluation of sodium nitroprusside for controlled hypotension in children during surgery. Front Pharmacol. 2015 Jul 6;6:136. doi: 10.3389/fphar.2015.00136. eCollection 2015. | |
| 23631460 | Derived | Hammer GB, Connolly SG, Schulman SR, Lewandowski A, Cohane C, Reece TL, Anand R, Mitchell J, Drover DR. Sodium nitroprusside is not associated with metabolic acidosis during intraoperative infusion in children. BMC Anesthesiol. 2013 Apr 30;13:9. doi: 10.1186/1471-2253-13-9. |
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Of the 206 randomized participants, 3 discontinued pre-operatively and 203 participants completed the study and no patients discontinued the study post operative. Participants counted as completing the study may have stopped the blinded study drug period early but continued on to the open-label study drug period and follow-up period.
206 participants were randomized to be dosed with one of 4 differed SNP infusion rates.
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| ID | Title | Description |
|---|---|---|
| FG000 | 0.3 μg/kg/Min | Rate of SNP infusion during blinded study drug period Patients who were randomized and never received a dose of study drug did not contribute data to any analysis population. The following three analysis populations were included in the study: Intent-to-Treat Safety (ITT S) Population consisted of all consented and randomized patients who received any amount of study drug Intent-to-Treat Efficacy Evaluable (ITT E) Population consisted of randomized and treated patients who had a pre treatment Baseline MAP and a second MAP determined within 30 minutes of study drug infusion at the starting dose Intent-to-Treat Completer (ITT C) Population consisted of all randomized and treated patients who completed the 30-minute blinded study drug period. The ITT C population is indicated by the participants who completed 'period 2. P |
| FG001 | 1 μg/kg/Min | Rate of SNP infusion during blinded study drug period Patients who were randomized and never received a dose of study drug did not contribute data to any analysis population. The following three analysis populations were included in the study: Intent-to-Treat Safety (ITT S) Population consisted of all consented and randomized patients who received any amount of study drug Intent-to-Treat Efficacy Evaluable (ITT E) Population consisted of randomized and treated patients who had a pre treatment Baseline MAP and a second MAP determined within 30 minutes of study drug infusion at the starting dose Intent-to-Treat Completer (ITT C) Population consisted of all randomized and treated patients who completed the 30-minute blinded study drug period. The ITT C population is indicated by the participants who completed 'period 2. . |
| FG002 | 2 μg/kg/Min | Rate of SNP infusion during blinded study drug period Patients who were randomized and never received a dose of study drug did not contribute data to any analysis population. The following three analysis populations were included in the study: Intent-to-Treat Safety (ITT S) Population consisted of all consented and randomized patients who received any amount of study drug Intent-to-Treat Efficacy Evaluable (ITT E) Population consisted of randomized and treated patients who had a pre treatment Baseline MAP and a second MAP determined within 30 minutes of study drug infusion at the starting dose Intent-to-Treat Completer (ITT C) Population consisted of all randomized and treated patients who completed the 30-minute blinded study drug period. The ITT C population is indicated by the participants who completed 'period 2. |
| FG003 | 3 μg/kg/Min | Rate of SNP infusion during blinded study drug period Patients who were randomized and never received a dose of study drug did not contribute data to any analysis population. The following three analysis populations were included in the study: Intent-to-Treat Safety (ITT S) Population consisted of all consented and randomized patients who received any amount of study drug Intent-to-Treat Efficacy Evaluable (ITT E) Population consisted of randomized and treated patients who had a pre treatment Baseline MAP and a second MAP determined within 30 minutes of study drug infusion at the starting dose Intent-to-Treat Completer (ITT C) Population consisted of all randomized and treated patients who completed the 30-minute blinded study drug period. The ITT C population is indicated by the participants who completed 'period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study - Randomized to be Dosed |
|
| ||||||||||||||||||
| Blinded Treatment Phase-Randomized/Dosed |
|
211 participants were enrolled in the study; 206 were randomized, 5 discontinued preoperatively.
Of the 206, 3 discontinued preoperatively after randomization resulting in 203 participants who completed the study. These 203 participants constituted the baseline population.
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| ID | Title | Description |
|---|---|---|
| BG000 | 0.3 mcg/kg/Min | Infusion rate scheduled to be titrated during the blinded phase to 0.3 mcg/kg/min |
| BG001 | 1 mcg/kg/Min | Infusion rate scheduled to be titrated during the blinded phase to 1 mcg/kg/min |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Mean Arterial Pressure (MAP) From the Baseline MAP | From the Baseline MAP until the end of the blinded phase; scheduled for 30 min | Change from Baseline in MAP across the Sodium Nitroprusside (SNP) dose groups by mean at Baseline, 30 mins (LOCF), and change from Baseline for the ITT Efficacy Evaluable Population consisted of randomized and treated patients who had a pre-treatment Baseline MAP and a second MAP determined within 30 mins of study drug infusion at the starting dose | Posted | Mean | Standard Deviation | mm Hg | Approximately 30 minutes |
|
Adverse events were monitored throughout the first 4 stages stages (prestudy drug administration, Blinded period, Open period,Follow-up period) of the study totalling upto 16 days.Serious adverse events was monitored for additional 30 days after follow-up
Treatment-emergent AEs (TEAEs) were defined as an AE experienced by the patient that was either first observed after the initiation of study drug (blinded or open-label) or represented an exacerbation (usually in severity) of a pre existing condition observed prior to treatment.Serious Adverse events include AEs leading to study drug withdrawal
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 0.3 μg/kg/Min | Rate of SNP infusion during blinded study drug period |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 8.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 8.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Scott Schulman, MD | Duke University Medical Center | 919-681-4877 | schul003@mc.duke.edu |
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| ID | Term |
|---|---|
| D007022 | Hypotension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D009599 | Nitroprusside |
| ID | Term |
|---|---|
| D005292 | Ferricyanides |
| D003486 | Cyanides |
| D000838 | Anions |
| D007477 | Ions |
| D004573 |
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|
| 3 mcg/kg/min | Active Comparator | Infusion of Sodium Nitroprusside began only after a 5-minute period of stable anesthesia or sedation (no changes in dosages). The infusion rate during the blinded study drug period was increased in a step-wise fashion to the full dose rate as follows: 5 ± 1 minutes at 1/3 of the full rate; 5 ± 1 minutes at 2/3 of the full rate; and 20 minutes at the full dose rate (ie, 30 minutes total). The full infusion rate was 0.6 mL/kg/hr; 2/3 of the full rate was 0.4 mL/kg/hr; and 1/3 of the full rate was 0.2 mL/kg/hr. After titration to the full dose of blinded study drug, blinded infusion dosage adjustments were not permitted during the blinded study drug administration period. The blinded infusion dosage continued for the 30 minutes unless clinical events demanded a change for safety reasons |
|
|
|
| Nitroprusside | Drug | Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS. |
|
|
| Nitroprusside | Drug | Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS. |
|
|
| Nitroprusside | Drug | Study drug was infused via a dedicated peripheral intravenous catheter or via a dedicated lumen of a multi-orifice central venous catheter. Infusion pumps capable of reliable delivery at low infusion rates (to 0.1 mL/hr) were used.Study drug was dispensed to the sites in 2 mL vials containing 25 mg/mL of sodium nitroprusside. The pharmacist prepared and dispensed the study drug, and supplied blinded study drug for each subject according to a randomization assignment generated by the IVRS |
|
|
Infusion rate of sodium nitroprusside at which a predetermined clinically meaningful target value (+/- 10%) of MAP was achieved during study drug administration |
| Up to the end of open label treatment (Approximately 120 minutes) |
| Number of Participants Who Reach Target MAP; | Blinded Study Drug Administration Period: Started with study drug administration following stabilization of anesthesia. Patients were administered a blinded dose of SNP for up to 30 mins. This period ended at the start of open-label study drug infusion or at the completion of the blinded infusion if no open-label study drug was given. The follow-up period immediately followed for those patients not receiving open-label infusion. Blinded Treatment Phase II - gap between the end of blinded study drug infusion and the start of open-label study drug infusion Open-label treatment phase began with the start of open-label study drug infusion and was at least 90 mins in duration. SNP was initiated at a dose deemed appropriate by the investigator and was gradually adjusted to reach a target MAP based on clinical presentation and needs of the patient. Target MAP was not to be < 50 mmHg (40 mmHg for patients < 30 days of age). This period ended at the completion of open-label infusion. | To the end of open label treatment (approximately 120 minutes) |
| COMPLETED |
|
| NOT COMPLETED |
|
| BG002 | 2 mcg/kg/Min | Infusion rate scheduled to be titrated during the blinded phase to 2 mcg/kg/min |
| BG003 | 3 mcg/kg/Min | Infusion rate scheduled to be titrated during the blinded phase to 3 mcg/kg/min |
| BG004 | Total | Total of all reporting groups |
| Months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
Rate of SNP infusion during blinded study drug period
| OG002 | 2 mcg/kg/Min | Rate of SNP infusion during blinded study drug period |
| OG003 | 3 mcg/kg/Min | Rate of SNP infusion during blinded study drug period |
| OG004 | Total | Total result |
|
|
|
| Primary | Overall Summary of Tolerability/Adverse Events (AEs) for ITT Safety Population | Treatment-emergent AEs (TEAEs) were defined as an AE experienced by the patient that was either first observed after the initiation of study drug (blinded or open-label) or represented an exacerbation (usually in severity) of a pre existing condition observed prior to treatment. Subjects will be followed for 30 days after discontinuation of study drug. The occurrence of Serious Adverse Events (SAEs) will be monitored for 30 days. | ITT Safety Population consisted of all consented and randomized patients who received any amount of study medication | Posted | Number | participants | 30 days |
|
|
|
| Secondary | Change From Baseline MAP Nitroprusside Infusion During the Blinded Infusion; | Change From Baseline in MAP (mmHg) After 20 and 25 Minutes Double-Blind Infusion (Overall) for ITT Efficacy Evaluable Population. | ITT Efficacy Evaluable Population consisted of randomized and treated patients who had a pre-treatment Baseline MAP and a second MAP determined within 25 minutes of study drug infusion at the starting dose. | Posted | Mean | Standard Deviation | mm Hg | 25 minutes |
|
|
|
| Secondary | Infusion Rate of Sodium Nitroprusside That Reduces MAP to a Predetermined Clinically Meaningful Target Value +/- 10%; | Infusion rate of sodium nitroprusside at which a predetermined clinically meaningful target value (+/- 10%) of MAP was achieved during study drug administration | The Analysis population included the participants in the ITT Efficacy evaluable population who achieved target MAP. ITT Efficacy Evaluable Population consisted of randomized and treated patients who had a pre-treatment Baseline MAP and a second MAP determined within 30 minutes of study drug. | Posted | Mean | Standard Deviation | mcg/kg/min | Up to the end of open label treatment (Approximately 120 minutes) |
|
|
|
| Secondary | Number of Participants Who Reach Target MAP; | Blinded Study Drug Administration Period: Started with study drug administration following stabilization of anesthesia. Patients were administered a blinded dose of SNP for up to 30 mins. This period ended at the start of open-label study drug infusion or at the completion of the blinded infusion if no open-label study drug was given. The follow-up period immediately followed for those patients not receiving open-label infusion. Blinded Treatment Phase II - gap between the end of blinded study drug infusion and the start of open-label study drug infusion Open-label treatment phase began with the start of open-label study drug infusion and was at least 90 mins in duration. SNP was initiated at a dose deemed appropriate by the investigator and was gradually adjusted to reach a target MAP based on clinical presentation and needs of the patient. Target MAP was not to be < 50 mmHg (40 mmHg for patients < 30 days of age). This period ended at the completion of open-label infusion. | ITT Efficacy Evaluable Population consisted of randomized and treated patients who had a pre-treatment Baseline MAP and a second MAP determined within 30 minutes of study drug | Posted | Number | participants | To the end of open label treatment (approximately 120 minutes) |
|
|
|
| 24 |
| 50 |
| 50 |
| 50 |
| EG001 | 1 μg/kg/Min | Rate of SNP infusion during blinded study drug period | 22 | 49 | 49 | 49 |
| EG002 | 2 μg/kg/Min | Rate of SNP infusion during blinded study drug period | 18 | 53 | 53 | 53 |
| EG003 | 3 μg/kg/Min | Rate of study drug infusion during blinded study drug period | 20 | 51 | 51 | 51 |
| Pancreatitis | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pseudocyst | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Postoperative Infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Serratia Infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Cerebrospinal fluid Leakage | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Infusion site extravasation | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Operative Haemorrhage | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Post procedural complication | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Post procedural discharge | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Blood Pressure decreased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Cardiac output decreased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Central Venous pressure increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Cauda Equina Syndrome | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypotonic Urinary Bladder | Renal and urinary disorders | MedDRA 8.1 | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Rebound Hypertension | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Superior mesenteric artery syndrome | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Heart Rate increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Coagulopathy | Blood and lymphatic system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 8.1 | Systematic Assessment |
|
| Eye Swelling | Eye disorders | MedDRA 8.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Face Oedema | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Blood Pressure Increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Urine Output decreased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Acidosis | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Metabolic Acidosis | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Periorbital Oedema | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Rebound Hypertension | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Swelling Face | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
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Not provided
| Electrolytes |
| D007287 | Inorganic Chemicals |
| D005290 | Ferric Compounds |
| D058085 | Iron Compounds |
| D006856 | Hydrogen Cyanide |
| D017672 | Nitrogen Compounds |
| N of participants with at least one TESAE |
|
| N with TEAE leading to study drug withdrawal |
|
| N of participants with MILD TEAE |
|
| N of participants with MODERATE TEAE |
|
| N of participants with SEVERE TEAE |
|
| N of participants with probably related TEAE |
|
| N of participants with possibly related TEAE |
|
| N of participants with Probably NOT related TEAE |
|
| N of participants with NOT related TEAE |
|
| N of Deaths |
|
|
| 20 Mins Observed (n = 42,27,19,26,114) |
|
|
| Change from BL - 20 mins (n = 42,27,19,26,114) |
|
|
| 25 mins observed (n = 39,24,15,20,98) |
|
|
| Change from BL - 25 mins (n = 39,24,15,20,98) |
|
|
| Did NOT achieve target MAP |
|
| Not determined |
|
| Achieved during the blinded treatment |
|
| Achieved during Blinded Phase II |
|
| Achieved during Open-label Treatment |
|