Trial Outcomes & Findings for An Observational Study on Real-world Use and Outcomes of Patients Treated With Tolvaptan for Hyponatraemia Due to SIADH (NCT NCT02545101)

NCT ID: NCT02545101

Last Updated: 2018-03-07

Results Overview

The primary variable of the study was the change in sodium levels from baseline to discharge or the final available measurement for patients who were not discharged (up to 6 weeks after treatment initiation).

• Recruitment status: COMPLETED
• Target enrollment: 100 participants
• Primary outcome timeframe: From Baseline Up to discharge (or a maximum of 6 weeks after start of treatment)
• Results posted on: 2018-03-07

Participant Flow

Participant milestones

Measure	Tolvaptan Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Overall Study STARTED	100
Overall Study COMPLETED	100
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

number of patients meeting the criterion

Baseline characteristics by cohort

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Age, Continuous	73.9 years STANDARD_DEVIATION 14.41 • n=100 Participants
Sex: Female, Male Female	53 Participants n=100 Participants
Sex: Female, Male Male	47 Participants n=100 Participants
Region of Enrollment Germany	44 participants n=100 Participants
Region of Enrollment Spain	56 participants n=100 Participants
Weight	68.8 kg STANDARD_DEVIATION 15.03 • n=89 Participants • number of patients meeting the criterion
Height	1.632 meters STANDARD_DEVIATION 0.0831 • n=89 Participants • number of patients meeting the criterion
Body Mass Index	25.781 Kg/m^2 STANDARD_DEVIATION 5.2890 • n=89 Participants • number of patients meeting the criterion.

PRIMARY outcome

Timeframe: From Baseline Up to discharge (or a maximum of 6 weeks after start of treatment)

Population: Baseline sodium level was not available for 4 patients

The primary variable of the study was the change in sodium levels from baseline to discharge or the final available measurement for patients who were not discharged (up to 6 weeks after treatment initiation).

Outcome measures

Measure	Tolvaptan n=96 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Change in Sodium Levels From Start of Treatment With Tolvaptan Until Hospital Discharge	10.3 mmol/L Standard Deviation 6.42

SECONDARY outcome

Timeframe: From Baseline (treatment initiation with tolvaptan) up to 24 hours afterwards

Population: Only patients with a value at both baseline and 24 hours of initiation of tovaptan were included in the change from baseline

Change in sodium level from last value prior to receiving tolvaptan until last available measurement within 24 hours of initiation of tolvaptan

Outcome measures

Measure	Tolvaptan n=95 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Change in Sodium Levels 24 Hours After Treatment Initiation	3.3 mmol/L Standard Deviation 4.53

SECONDARY outcome

Timeframe: From Baseline (treatment initiation with tolvaptan) up to 6 weeks afterwards

Population: only patients with a value at both baseline and that time point are included in the change

Change in sodium level from last value prior to receiving tolvaptan until last available measurement up to week 6

Outcome measures

Measure	Tolvaptan n=96 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Change in Sodium Levels 6 Weeks After Treatment Initiation	11.8 mmol/L Standard Deviation 6.45

SECONDARY outcome

Timeframe: From Baseline (treatment initiation with tolvaptan) up to 6 weeks afterwards

Population: Exact time was available for 64 patients, so the analysis "in hours" had a n=64

Time (hours) to sodium normalisation, defined as a serum sodium level > 135 mmol/L, by evaluation of serum sodium levels in relation to the episode of hyponatraemia secondary to SIADH being captured in the study (up to 6 weeks after treatment initiation).

Outcome measures

Measure	Tolvaptan n=64 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Time (Hours) to Sodium Normalisation	115.5 hours Interval 72.0 to 187.0

SECONDARY outcome

Timeframe: Baseline

Primary disease diagnoses leading to SIADH by evaluation of diagnosis information in relation to the episode of hyponatraemia being captured in the study from the patient's medical records

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Percentage of Participants Distributed by the Primary Disease Diagnoses Leading to SIADH (Cancer, Pulmonary Disease, CNS Disorder, Etc.,) Cancer	27 % of participants
Percentage of Participants Distributed by the Primary Disease Diagnoses Leading to SIADH (Cancer, Pulmonary Disease, CNS Disorder, Etc.,) Medication	20 % of participants
Percentage of Participants Distributed by the Primary Disease Diagnoses Leading to SIADH (Cancer, Pulmonary Disease, CNS Disorder, Etc.,) CNS disorder	11 % of participants
Percentage of Participants Distributed by the Primary Disease Diagnoses Leading to SIADH (Cancer, Pulmonary Disease, CNS Disorder, Etc.,) Pulmonary disease	7 % of participants
Percentage of Participants Distributed by the Primary Disease Diagnoses Leading to SIADH (Cancer, Pulmonary Disease, CNS Disorder, Etc.,) Hereditary causes	3 % of participants
Percentage of Participants Distributed by the Primary Disease Diagnoses Leading to SIADH (Cancer, Pulmonary Disease, CNS Disorder, Etc.,) Other (mainly unknown/idiopathic origin)	32 % of participants

SECONDARY outcome

Timeframe: Baseline

symptoms associated with hyponatraemia by evaluation of symptomatology information in relation to the episode of hyponatraemia being captured in the study from the patient's medical records

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Symptoms Associated With Hyponatraemia (Number of Symptomatic/Asymptomatic Patients in the Study Population)	83 Participants

SECONDARY outcome

Timeframe: Baseline

specialty of the clinician prescribing tolvaptan by evaluation of details of the physician who prescribed tolvaptan for the episode of hyponatraemia being captured in the study from the patient's medical records

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Percentage of Participants Distributed by the Specialties of Their Clinicians Prescribing Tolvaptan (e.g., Endocrinologists, Nephrologists, Oncologists, Etc.,) Endocrinology	40 % of participants
Percentage of Participants Distributed by the Specialties of Their Clinicians Prescribing Tolvaptan (e.g., Endocrinologists, Nephrologists, Oncologists, Etc.,) Nephrology	25 % of participants
Percentage of Participants Distributed by the Specialties of Their Clinicians Prescribing Tolvaptan (e.g., Endocrinologists, Nephrologists, Oncologists, Etc.,) Internal medicine	19 % of participants
Percentage of Participants Distributed by the Specialties of Their Clinicians Prescribing Tolvaptan (e.g., Endocrinologists, Nephrologists, Oncologists, Etc.,) Emergency Room Dept	6 % of participants
Percentage of Participants Distributed by the Specialties of Their Clinicians Prescribing Tolvaptan (e.g., Endocrinologists, Nephrologists, Oncologists, Etc.,) Oncology	5 % of participants
Percentage of Participants Distributed by the Specialties of Their Clinicians Prescribing Tolvaptan (e.g., Endocrinologists, Nephrologists, Oncologists, Etc.,) Other	5 % of participants

SECONDARY outcome

Timeframe: From Baseline (treatment initiation with tolvaptan) up to 6 weeks afterwards

Average daily dose of tolvaptan used and treatment duration (expressed in days) for the episode of hyponatraemia secondary to SIADH being captured in the study by evaluation of dosing information (and dates) from the patient's medical records (up to 6 weeks after the initiation of tolvaptan treatment).

For these outcome measures, only days on treatment were considered (e.g. if tolvaptan treatment was interrupted and resumed afterwards, the days withot treatment were not considered).

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Average Daily Dose of Tolvaptan Used and Treatment Duration (Expressed in Days) for the Episode of Hyponatraemia Being Captured in the Study	12.67 mg Standard Deviation 9.173

SECONDARY outcome

Timeframe: From Baseline (treatment initiation with tolvaptan) up to 6 weeks afterwards

Time (days) to sodium normalisation, defined as a serum sodium level > 135 mmol/L, by evaluation of serum sodium levels in relation to the episode of hyponatraemia secondary to SIADH being captured in the study (up to 6 weeks after treatment initiation).

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Time (Days) to Sodium Normalisation	7 days Interval 5.0 to 10.0

SECONDARY outcome

Timeframe: Baseline

symptoms associated with hyponatraemia by evaluation of symptomatology information in relation to the episode of hyponatraemia being captured in the study from the patient's medical records

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia confusion	28 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia lethargy	41 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia gait disorder	37 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia nausea	33 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia disorientation	31 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia drowsiness	30 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia anorexia	28 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia vomiting	24 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia restlessness	15 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia brain damage	10 Participants
Number of Participants With Presence of Different Symptoms Associated With Hyponatraemia headache	10 Participants

SECONDARY outcome

Timeframe: From Baseline (treatment initiation with tolvaptan) up to 6 weeks afterwards

Average treatment duration for the episode of hyponatraemia secondary to SIADH being captured in the study by evaluation of dosing information (and dates) from the patient's medical records (up to 6 weeks after the initiation of tolvaptan treatment).

For these outcome measures, only days on treatment were considered (e.g. if tolvaptan treatment was interrupted and resumed afterwards, the days withot treatment were not considered).

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Average Treatment Duration for the Episode of Hyponatraemia Being Captured in the Study	27.96 days Standard Deviation 16.479

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline (tolvaptan treatment initiation) up to 6 weeks after treatment initiation

Only medications taken by more than 5% of the study population are presented

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Acetylsalicylic acid	27 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Omeprazole	25 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Amlodipine	23 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Ramipril	18 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Dexomethasone	15 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Pantoprazole	15 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Enoxaparin	14 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Lorazepam	14 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Metamizole	13 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Simvastatin	13 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Acetominophen	11 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Levothyroxine	10 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Metformin	10 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Enalapril	10 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Torasemide	8 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Ondansetron	8 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Fursosemide	7 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Insulin	7 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Levetiracetam	7 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Lactulose	7 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Atorvastatin	7 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Metoprolol succinate	7 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Metoclopramide	7 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Bisoprolol	6 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Metoprolol	6 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Normal saline	6 Participants
Concomitant Treatments to Tolvaptan (Number and Percentage of Subjects Taking Concomitant Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Salbutamol	6 Participants

POST_HOC outcome

Timeframe: From Baseline (treatment initiation with tolvaptan) up to 6 weeks afterwards

Population: Originally, the idea was to analyse this out come in "hours", but due to missing data, it was also analysed in "days".

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Time (Days) to Hospital Discharge up to 6 Weeks After Treatment Start	7.0 days Interval 6.0 to 9.0

OTHER_PRE_SPECIFIED outcome

Timeframe: From 12 months up to baseline (tolvaptan treatment initiation)

Only medications taken by more than 5% of the study population are presented

Outcome measures

Measure	Tolvaptan n=100 Participants Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Prior Treatments Before Tolvaptan (Number and Percentage of Subjects Taking Prior Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Furosemide	10 Participants
Prior Treatments Before Tolvaptan (Number and Percentage of Subjects Taking Prior Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Levofloxavin	7 Participants
Prior Treatments Before Tolvaptan (Number and Percentage of Subjects Taking Prior Medications Will be Summarized by Anatomical Therapeutic Chemical (ATC) Classification) Normal Saline	6 Participants

Adverse Events

Tolvaptan

Serious events: 10 serious events

Other events: 12 other events

Deaths: 3 deaths

Serious adverse events

Measure	Tolvaptan n=100 participants at risk Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
Infections and infestations WOUND INFECTION	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Metabolism and nutrition disorders HYPONATRAEMIA	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Infections and infestations URINARY TRACT INFECTION	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
General disorders DEATH	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Investigations BLOOD SODIUM INCREASED	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Blood and lymphatic system disorders NEUTROPENIA	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	2.0% 2/100 • Number of events 2 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Nervous system disorders EPILEPSY	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SMALL CELL LUNG CANCER	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Nervous system disorders SYNCOPE	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Infections and infestations MENINGITIS	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.

Other adverse events

Measure	Tolvaptan n=100 participants at risk Adult patients who received at least 2 doses of tolvaptan for the treatment of one occurrence of hyponatraemia secondary to SIADH.
General disorders THIRST	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Infections and infestations EAR INFECTION	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Infections and infestations ORAL CANDIDIASIS	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Infections and infestations HERPES ZOSTER	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Hepatobiliary disorders CHOLANGITIS ACUTE	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Investigations BLOOD SODIUM DECREASED	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Investigations BLOOD SODIUM ABNORMAL	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Gastrointestinal disorders DIARRHOEA	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Metabolism and nutrition disorders DIABETES MELLITUS	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Vascular disorders HYPOTENSION	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Investigations BLOOD SODIUM INCREASED	2.0% 2/100 • Number of events 2 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Nervous system disorders CEREBROVASCULAR ACCIDENT	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Nervous system disorders SEIZURE	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.
Infections and infestations CYSTITIS	1.0% 1/100 • Number of events 1 • Study period was defined for each patient as: from start of tolvaptan treatment until 6 weeks afterwards maximum. Treatment-emergent adverse event defined as adverse event (AEs) that started or worsened after the start of the administration of tolvaptan, i.e. meaning temporal association but not necessarily causality/relationship (investigators were not asked about this). Please note that collection of AE, as the study itself, was retrospective.

Additional Information

Medical Department

Otsuka Pharmaceutical Europe Ltd.

Phone: +44(0)2037475000

Results disclosure agreements

• Principal investigator is a sponsor employee As a multicentre study, the first publication shall be based on consolidated analysed data from all centres, i.e. the publication of results from individual institution/Investigator is not allowed before the publication of the full study results. The PI agrees to give the sponsor 60 days to review the communications. If case of propietary information inadvertenly divulged, intellectual property rights at risk or inaccurate information presented, changes can be required by the sponsor.
• Publication restrictions are in place

Restriction type: OTHER