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Diabetes Mellitus, Type 2Phase 4NCT04978649

Intervention for High-normal Blood Pressure in Adults With Type 2 Diabetes-----renal Substudy

A Phase 4 study testing Allisartan Isoproxil and Amlodipine in people with Diabetes Mellitus, Type 2 and Blood Pressure, run by Guangdong Provincial People's Hospital.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Lowering of blood pressure (BP) in high-risk hypertensive individuals reduces major adverse cardiovascular (CV) and renal events. Diabetic patients with hypertension benefit from BP lowering treatment. Read more about this study

Who is it for?
Ages 45 to 79 years
Conditions the study is for
Diabetes Mellitus, Type 2, Blood Pressure
What is being tested?
Allisartan Isoproxil and Amlodipine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
1 Sep 2021to 31 Jul 2028
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • irrespective of sex;
  • aged between 45 and 79 years;
  • with office-measured seated BP 120-139 mm Hg systolic and below 90 mm Hg diastolic;
  • diagnosed of type 2 diabetes mellitus (T2DM), currently on diabetic therapy; a glycosylated hemoglobin (HbA1c) ≤ 8.5%;
  • informed consent provided and long-term follow-up possible

Who cannot join

  • administration of any antihypertensive medications within 1 month;
  • a history of hypoglycemic coma / seizure;
  • confirmed diagnosis of type 1 diabetes mellitus;
  • alanine-aminotransferase (ALT) or aspartate-aminotransferase (AST) over three times the upper limit of normal;
  • estimated glomerular filtration rate < 45 ml/min/1.73m2;
  • a history of congestive heart failure with left ventricular ejection fraction < 40%, requiring treatment with renin-angiotensin system (RAS) blockers; coronary artery disease requiring RAS blockers for secondary prevention;
Show all 17Show fewer
  • acute on-set of stroke within 6 months prior to randomization;
  • a ratio of urinary albumin (in mg/L) to urinary creatinine (in g/L) (ACR) ≥ 300 mg/g;
  • a history of primary or secondary renal diesease requiring a therapy using glucocorticoid or immunity inhibitor;
  • a history of polycystic kidney;
  • known contraindications for the active study medications;
  • a history of psychological or mental disorder;
  • pregnancy or currently planning to have babies or lactation;
  • severe diseases such as severe valvular heart diseases;
  • an expected residual life span less than 3 years;
  • a malignancy that clinical investigators consider as unsuitable to participate;
  • currently participating in another clinical trial.

About this study

Lowering of blood pressure (BP) in high-risk hypertensive individuals reduces major adverse cardiovascular (CV) and renal events. Diabetic patients with hypertension benefit from BP lowering treatment. The present trial, IPAD-CKD in brief, is a randomized, open-label, parallel-designed, multicenter study involving nearly 5322 patients to be recruited over three years and to be followed up for a median of four years and a half. IPAD-CKD tests the hypothesis that antihypertensive medications in adults with type 2 diabetes, whose seated BP 120-139 mm Hg systolic and below 90 mm Hg diastolic, results in 20% difference in the incidence of major renal events. During follow-up for participants in the intensive group, the sitting systolic pressure should be decreased to below 120 mm Hg, by titration and combination of the double-blind study medications of an angiotensin type-1 receptor blocker Allisartan (240 mg/day), a dihydropyridine calcium-channel blocker (amlodipine 5-10 mg/day), and/or other medications if necessary. For those in the standard group, the sitting systolic pressure should be monitored and controlled below 140 mm Hg.

Read the detailed description

The IPAD-CKD trial is a randomized, open-label, parallel-designed, multicenter study. 5322 patients will be recruited over three years with a median follow up of 4.5 years. IPAD tests the hypothesis that intensive antihypertensive medical therapy in adult patients with type 2 diabetes, whose seated BP ranges from 120 to 139 mm Hg systolic and < 90 mm Hg diastolic, results in 20% reduction in the incidence of major renal events (the primary endpoint), a composite of renal failure and proteinuria progression. Secondary endpoints of this study include: renal failure ; proteinuria progression; proteinuria reversion; end stage renal disease; cardiovascular-cause mortality; MI; hospitalization for HF; stroke;hospitalization for unstable angina; all-cause mortality;development of diabetic retinopathy that needs interventional operation; peripheral arterial diseases; new on-set atrial fibrillation or flutter; cancer.

Inclusion criteria for the study include T2DM patients aged between 45 and 79 years within the aforementioned BP ranges. For participants in the intensive group, the sitting systolic BP should decrease to < 120 mm Hg, using titration and combination of study medications consisting of an angiotensin type-1 receptor blocker Allisartan (240 mg/day) and a dihydropyridine calcium-channel blocker (amlodipine 5-10 mg/day), and/or other medications if necessary.For those in the standard group, the sitting systolic pressure should be monitored and controlled below 140 mm Hg. Across the whole study, 310 primary endpoints are expected to occur. Interim analyses will be carried out on an intention-to-treat basis at the accumulation of 107 and 214 primary endpoints respectively. At the completion of the trial, both an intention-to-treat and a per-protocol analysis will be performed.

Being tested
Allisartan Isoproxil, Amlodipine
Keywords
prehypertension, renal disease
Medical subject headings
Diabetes Mellitus, Type 2, Prehypertension, Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allisartan IsoproxilDrug

    Also called Xinlitan

    Allisartan Isoproxil 240mg daily will be used to lower BP to below 120 mm Hg systolic.

  • AmlodipineDrug

    Also called Qiaohean

    Amlodipine 5mg daily will be added to Allisartan Isoproxil and afterwards increased to 10mg daily, if necessary to reach the blood pressure goal (below 120 mm Hg systolic).

Study groups in NCT04978649
Study groupRoleWhat they receive
intensive treatment groupActive comparatorReal antihypertensive agents will be provided for this arm, to decrease systolic BP to lower than 120 mm Hg. In this group, the following study medications will be used: tablets with Allisartan Isoproxil 240 mg (first-line medication); tablets with Amlodipine 5 mg (second-line medication). Treatment will be started with Allisartan 240 mg. If necessary to reach the BP goal, Amlodipine (first 5 mg or then 10 mg daily) will be given in addition. If intolerable side effects occur, first-line medication may be replaced by second-line medication.
Receives: Drug: Allisartan Isoproxil; Drug: Amlodipine
standard treatment groupPlacebo comparatorIn this arm participants are followed up and no medications be used until BP becomes ≥ 140 mm Hg systolic and/or 90 mm Hg diastolic. Medications are determined by investigators in lines with recommendations by current Chinese guidelines to decrease BP to lower than 140 mm Hg systolic and to lower than 90 mm Hg diastolic.
Receives: Drug: Allisartan Isoproxil; Drug: Amlodipine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of Major Renal Events

    The major renal events defined in the study include a composite of renal failure (defined as dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), or serum creatinine level >3.3 mg/dl, or a doubling of the serum creatinine level)and proteinuria progression(defined as:uACR ≥30 mg/gCr if baseline uACR< 30 mg/gCr; uACR ≥300 mg/gCr if baseline uACR is between 30 to 300 mg/gCr.

    )

    Measured: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months

Secondary outcomes (12)
  1. renal failure

    dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), or serum creatinine level >3.3 mg/dl, or a doubling of the serum creatinine level

    Measured: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months

  2. proteinuria progression

    uACR ≥30 mg/gCr if baseline uACR< 30 mg/gCr; uACR ≥300 mg/gCr if baseline uACR is between 30 to 300 mg/gCr.

    Measured: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months

  3. proteinuria reversion

    uACR <30mg/gCr if baseline uACR is between 30 to 300 mg/gCr.

    Measured: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months

  4. cardiovascular-cause mortality

    Cardiovascular death include death caused by stroke, MI, HF, sudden death or any other death attributed to cardiovascular diseases. Sudden death (ICD-Code I46.1, R96) encompasses any death of unknown origin occurring instantly or within an estimated 24 hours after the onset of acute symptoms as well as unattended death for which no likely cause can be established by autopsy or recent medical history.

    Measured: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months

  5. Acute Myocardial Infarction

    Acute myocardial infarction (MI) is defined when any one of the following criteria occurs. (1) Detection of a rise and/or fall of cardiac biomarker values, with at least one value above the 99th percentile upper reference limit and with at least one of the following manifestations: symptoms of ischaemia that should have lasted for at least 30 minutes and should not have been responsive to sublingual administration of nitrates; new or presumed new significant ST-segment-T wave changes or new left bundle branch block (LBBB); development of pathological Q waves in the ECG; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. (2) Identification of an intracoronary thrombus by angiography or autopsy. (3) Cardiac death with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG changes or new LBBB, but death occurred before cardiac biomarkers were obtained, or before cardiac biomarker values would be increased.

    Measured: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months

  6. Hospitalization of Congestive Heart Failure

    Congestive heart failure (HF) requires the presence of three conditions, namely symptoms, such as dyspnea, clinical signs, such as ankle edema or crepitations, and the necessity to initiate treatment with open-label diuretics, vasodilators or antihypertensive drugs. HF cases may also be adjudicated as chronic stable HF but this is not considered an outcome of the present study.

    Measured: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months

  7. Hospitalization of Unstable Angina

    Unstable angina is defined as new onset or worsening angina pectoris requiring hospitalization with angiographically documented coronary atherosclerosis or transient electrocardiographic changes of the ST-segment or T-wave without evidence for myocardial necrosis. This diagnosis excludes patients with angina pectoris admitted to the hospital only for investigation.

    Measured: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months

  8. All-cause Mortality

    All-cause mortality refers to death from any causes.

    Measured: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.

  9. Diabetic Retinopathy Requiring Interventional Operation or Surgery

    Diabetic retinopathy requiring interventional operation or surgery is defined as the confirmed diagnosis of diabetic retinopathy, indicated for interventional operation or surgery, which is documented by ophthalmologists.

    Measured: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.

  10. Peripheral Arterial Diseases Requiring Revascularization

    Peripheral arterial diseases requiring revascularization are defined as the confirmed diagnosis of any one of the peripheral arterial diseases indicated for revascularization.

    Measured: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.

  11. New Atrial Fibrillation or Flutter

    Atrial fibrillation or flutter is confirmed and documented with electrocardiogram indicating the occurence of atrial fibrillation or flutter. New development of atrial fibrillation or flutter is defined only if a participant at baseline has no history of and his or her electrocardiogram shows no signs of atrial fibrillation or flutter.

    Measured: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.

  12. Cancer

    Cancer defined in the present study is recorded only when there is pathologically confirmed evidence.

    Measured: Time Frame: From date of randomization until the date of death from any causes, assessed up to 60 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2021
  2. Study start1 Sep 2021 (estimated)
  3. Primary completion31 Jul 2026 (estimated)
  4. Study completion31 Jul 2028 (estimated)

Why it stopped: Cooperation plan has been changed

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04978649
Sponsor's protocol ID
GDPH-IPAD-CKD
Status last verified
Aug 2022
First submitted
20 Jul 2021
Last updated
26 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Allisartan Isoproxil and Amlodipine in people with Diabetes Mellitus, Type 2 and Blood Pressure, run by Guangdong Provincial People's Hospital.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 26 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of Major Renal Events (time frame: From date of randomization until the date of first documented incidence of the major renal events prespecified, whichever comes first, assessed up to 60 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2022.

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